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Lyme Endotoxins & Biotoxins

Some physician's feel that Lyme is like a donut covered in powder, but the powder is a biotoxin or "endotoxin." And some patients are very poor at removing these toxins. These biotoxins mess up hormones, mess up your weight, weaken you ability to fight infections and cancer, lower your natural pain killing endorphins, undermine sleep and thinking. These are just a few examples. The bottom line is that biotoxins can leave you very ill and in an unknown percentage can kill.

Sincere physicians treat many patients with antibiotics, and yet this releases biotoxins and endotoxins from the Lyme, and these are biologically active chemicals that effect genes and commonly increase weight, increase mood trouble, and increase inflammation and forty other problems.

My opinion is that it is a proven fact that Lyme has endotoxins in the small abstracts below. But what is an endotoxin?

Simply, they are substances on the outside of the lyme bug, in its outer shell, which is typically released when the lyme bug is disrupted or destroyed. Endotoxins are very active molecules that cause severe allergic reactions, fever and influence your immune system significantly. Some endotoxins are so strong they cause you to lose your blood pressure and die from the loss of blood to vital organs, or from severe diarrhea if the endotoxin is in the intestines. Obviously, Lyme's endotoxins do not act this particular way.

Endotoxins are a made of two parts: a fat or lipid bound to a polysaccharide chain in the lyme bug's outer shell. Endotoxins are like other biotoxins in that their goal is to help the bug survive. Some endotoxins are released in the body to make it safe for new lyme bugs, or when attacked by your immune system attack cells. The full actions and types of Lyme's biotoxins and endotoxins is unknown.

Biotoxins exist in many types of creatures: tetanus, botulinum (botox), spiders, algae, ascaridin (gut parasites), staph, strept, babasia, lyme, special fish, clamydia, tuberculosis, fungus or molds and viruses. Biotoxins are proposed to be tiny molecules used to survive by effecting the hostęs body in many ways that helps the infecting agent survive.

Labs that must be checked in all Lyme patients are:

  1. Leptin (LabCorp test code 146712)
  2. Alpha MSH or Melanocyte Stimulating Hormone (LabCorp test code 010421)
  3. Biotoxin Processing Genes: HLA DRB, DBQ Disease Evaluation (LabCorp test code 012542)

The last lab listed, or the HLA lab has been found to provide some specific genetic abilities to removal Lyme toxins. Our new Mold Warrior book has the table that shows which people have trouble removing Lyme biotoxins -- so they just float around the body forever messing up DNA and the body.

MSH is a massively critical hormone that will be a hot new treatment in future years and help with acne, obesity, addiction, sleep, fatigue, etc. If your MSH is low you clearly have massive toxins or inflammation that is at a dangerous level. You will need treatment with someone with is up on this 2006 medicine.

Leptin helps you see if the biotoxins have messed with the fat cells. It is a sign common in Lyme biotoxins and massive inflammation. (Reading it is complex.).

Studies on clearly positive Lyme patients show a simple biotoxin binder that NEVER leaves the intestines improves the patient's health and they do better in brain tests that measure biotoxin disease. Most initially get much sicker as the fat-loving biotoxin is pulled out into the blood stream and inflames the body, but over many weeks or months they clearly improve -- with no antibiotic. Most have had extensive lyme killing antibiotics already. Of course, the biotoxin binder needs to be used at high doses or it is a false trial -- like licking an aspirin and expecting arthritis relief.

Of course, their improvement assumes they are not living in a home with toxic mold all over the walls, or hidden behind a wall. This has actually happened when someone is not getting better. I ask about the possibility of indoor mold and they say, "Oh, we killed all that stuff under our floors last year with some bleach and changing a few boards." I just shake my head. They sincerely do not understand that some indoor mold chemicals are biowarfare agents -- we are not talking about the 100,000 to 200,000 safe forms outside. They were not getting better and we found toxic mold species at work or home.

According to Internist and author, Dr. James Howenstine, Lyme disease "requently exhibits neurologic abnormalities because the Lyme neurotoxins are drawn to the fatty tissue found in the brain and peripheral nerves. As a consequence sudden deafness, Bells palsy, Parkinson's Disease, Multiple Sclerosis, reflex sympathetic dystrophy, peripheral neuritis, and chronic pain may appear."

ARTICLE ABSTRACTS POINTING TO
POSSIBLE ACTIVE PROTEINS OR
TOXINS COMING FROM LYME

All bolding italics are from me


23: Zentralbl Bakteriol Mikrobiol Hyg [A]. 1986 Dec;263(1-2):137-41.

Borrelia burgdorferi lipopolysaccharide and its role in the pathogenesis of Lyme disease.

Habicht GS, Beck G, Benach JL, Coleman JL.

Lipopolysaccharides (LPS) are a constitutive part of the outer wall of gram negative bacteria. Because many of the symptoms of Lyme disease could be explained by a spirochetal LPS we have subjected Borrelia burgdorferi to standard LPS extraction techniques which yielded a LPS which accounted for 1.5-4% of the dry weight. The LPS was very similar to classical gram negative bacterial LPS both chemically and in its biological activities which included pyrogenicity, mitogenicity for lymphocytes and the induction of Interleukin 1 production by macrophages. In addition, the LPS produced an acute inflammatory reaction when injected intradermally into rabbit skin. It could also prepare a skin site for the production of the local Shwartzman reaction. These results show that the Lyme disease spirochete contains a hitherto unknown LPS that is biologically active in vitro and in vivo. It is likely that this molecule plays an important role in the pathogenesis of Lyme disease.

PMID: 3577475 [PubMed - indexed for MEDLINE]


41: J Infect Dis. 1985 Jul;152(1):108-17.

Chemical and biologic characterization of a lipopolysaccharide extracted from the Lyme disease spirochete (Borrelia burgdorferi).

Beck G, Habicht GS, Benach JL, Coleman JL.

A lipopolysaccharide (LPS) was isolated from the Lyme disease spirochete by a modification of the hot phenol-water method. The material was composed of 45% carbohydrate, 8% protein, 44% lipid A, and 1% 3-deoxy-D-mannooctulosonic acid and accounted for approximately 1.5% of the cellular dry weight. The isolated LPS possessed several biologic activities characteristic of endotoxins. The LPS was pyrogenic for rabbits, mitogenic for human mononuclear cells and murine splenocytes, capable of clotting limulus lysate, and cytotoxic for murine macrophages. LPS extracted from Borrelia burgdorferi by the petroleum-ether:chloroform:liquid-phenol procedure was also characterized. The results show that the Lyme disease spirochete contains a hitherto unknown LPS that is biologically active in vitro, and the expression of such activities in vivo may play an important role in the pathogenesis of Lyme disease. Some of the clinical manifestations of other spirochetal disease may be explained by similar endotoxins in those organisms. To our knowledge this is the first report of an LPS extracted from a spirochete that is known to be a human pathogen.

PMID: 4008983 [PubMed - indexed for MEDLINE]


22: Zentralbl Bakteriol Mikrobiol Hyg [A]. 1986 Dec;263(1-2):142-5.

Endotoxin-like activity associated with Lyme disease Borrelia.

Fumarola D, Munno I, Marcuccio C, Miragliotta G.

The newly recognized spirochete, Borrelia burgdorferi, the causative agent of Lyme Disease, has been examined for endotoxin-like activities as measured by the standard Farmacopea Ufficiale della Republica Italiana rabbit fever test and the Limulus amoebocyte lysate assay. The suspension of heat-killed microorganism caused a febrile response at a dose of 1 X 10(8) bacteria pro kilo. Similar results were obtained in the Limulus assay where the heat-killed spirochetes stimulated formation of solid clot until the concentration of 1 X 10(5) per ml. Both in pyrogen test and in Limulus assay heat-killed Escherichia coli exhibited a higher degree of potency. These results show that LD-Borrelia possess endotoxin-like activities which could help in understanding the pathogenesis of the clinical symptomatology of the disease.

PMID: 3577476 [PubMed - indexed for MEDLINE]


Immunology. 2004 Nov;113(3):401-8.

Characterization of the B-cell inhibitory protein factor in Ixodes ricinus tick saliva: a potential role in enhanced Borrelia burgdoferi transmission.

Hannier S, Liversidge J, Sternberg JM, Bowman AS.

School of Biological Science, Zoology, University of Aberdeen, UK.

We recently described the inhibition of host B lymphocytes by Ixodes ricinus tick saliva. In this study, we characterized the factor responsible for this activity and examined the modulation of lipopolysaccharide (LPS)- and Borrelia burgdorferi outer surface protein (Osp)-induced proliferation of naive murine B lymphocytes by an enriched fraction of this factor. The B-lymphocyte inhibitory activity was destroyed by trypsin treatment, indicating that a proteinaceous factor was responsible for this activity. The removal of glutathione-S-transferase (GST) from tick salivary glands extracts (SGE) showed that this B-cell inhibitory protein (BIP) was not a GST. Gel filtration liquid chromatography indicated that BIP has a native molecular weight of approximately 18,000. An enrichment protocol, using a combination of anion-exchange and reverse-phase liquid chromatography, was established. BIP-enriched fractions did not suppress T-cell proliferation. Delayed addition of BIP-enriched fractions, up to 7 hr after LPS addition, inhibited the proliferation of isolated B cells. BIP-enriched fractions dramatically inhibited both OspA- and OspC-induced proliferation of isolated B cells. These results strongly suggest that BIP may facilitate B. burgdorferi transmission by preventing B-cell activation, and also highlights the potential of BIP as a therapeutic agent in B-cell maladies.

PMID: 15500628 [PubMed - indexed for MEDLINE]


2: Arthritis Rheum. 2004 Jul;50(7):2360-9.

Outer surface lipoproteins of Borrelia burgdorferi vary in their ability to induce experimental joint injury.

Batsford S, Dunn J, Mihatsch M.

Albert Ludwigs University, Freiburg, Germany. bats@ukl.uni-freiburg.de

To examine the ability of bacterial lipoproteins from the spirochete Borrelia burgdorferi to cause in vivo tissue injury (arthritis). METHODS: Outer surface proteins (OSPs) from B burgdorferi were used in a rat model of antigen-induced allergic arthritis. Intraarticular challenge with recombinant OspA, OspB, and OspC in nonlipidated (peptide) and lipidated forms was performed in the left knee joint; the contralateral joint received buffer as control. Inflammation was monitored by technetium scintigraphy and histology. RESULTS: Nonlipidated (peptide) OspA, OspB, and OspC did not induce arthritis; the only exception was polymerized OspA, which was tested in preimmunized rats. Lipidated OspA from 2 different strains and lipidated OspC induced severe arthritis, whereas lipidated OspB failed to induce injury. A synthetic analog of the OSP lipid modification, lipopeptide Pam(3)Cys-Ser-Lys(4)-OH, either alone or coupled to bovine serum albumin, also failed to induce injury. Injury did not develop in control groups that were given the appropriate buffers or lipopolysaccharide. This showed that lipidated borrelial OSPs can be potent arthritogens but vary greatly with respect to their injury-inducing potential. The possession of a lipid modification is essential but is not sufficient to render an OSP arthritogenic. CONCLUSION: This is the first study to demonstrate that individual lipoproteins from B burgdorferi can induce experimental joint injury in vivo. These results may help elucidate the pathogenesis of Lyme arthritis and, above all, underline the importance of bacterial lipoproteins as major virulence factors.

PMID: 15248237 [PubMed - indexed for MEDLINE]


12: J Immunol. 2001 Jan 1;166(1):473-80.

Borrelia burgdorferi and other bacterial products induce expression and release of the urokinase receptor (CD87).

Coleman JL, Gebbia JA, Benach JL.

State of New York Department of Health, State University of New York, Stony Brook, NY 11794-5120, USA. jcoleman@notes.cc.sunysb.edu

The urokinase-type plasminogen activator receptor (uPAR, CD87) is a highly glycosylated 55- to 60-kDa protein anchored to the cell membrane through a glycosylphosphatidylinositol moiety that promotes the acquisition of plasmin on the surface of cells and subsequent cell movement and migration by binding urokinase-type plasminogen activator. uPAR also occurs in a soluble form in body fluids and tumor extracts, and both membrane and soluble uPAR are overexpressed in patients with tumors. uPAR may be a factor in inflammatory disorders as well. We investigated whether Borrelia burgdorferi could stimulate up-regulation of cell membrane uPAR in vitro. B. burgdorferi, purified native outer surface protein A, and a synthetic outer surface protein A hexalipopeptide stimulated human monocytes to up-regulate membrane uPAR as measured by immunofluorescence/FACS and Western blot. The presence of soluble uPAR in culture supernatants, measured by Ag capture ELISA, was also observed. LPS from Salmonella typhimurium and lipotechoic acid from Streptococcus pyogenes also induced the up-regulation of both membrane and soluble uPAR protein by monocytes. Up-regulation of uPAR was induced by conditioned medium from B. burgdorferi/monocyte cocultures. The up-regulation of uPAR by B. burgdorferi was concomitant with an increase in uPAR mRNA, indicating that synthesis was de novo. The expression and release of uPAR in response to B. burgdorferi and other bacterial components suggests a role in the pathogenesis of Lyme disease as well as in other bacterial infections.

PMID: 11123326 [PubMed - indexed for MEDLINE]


13: Infect Immun. 2000 Dec;68(12):6663-9.

Interleukin-10 modulates proinflammatory cytokines in the human monocytic cell line THP-1 stimulated with Borrelia burgdorferi lipoproteins.

Murthy PK, Dennis VA, Lasater BL, Philipp MT.

Department of Parasitology, Tulane Regional Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana 70433, USA.

We determined previously that lipoproteins of Borrelia burgdorferi stimulate inflammatory and anti-inflammatory cytokines (interleukin-10 [IL-10]) in monocytes. IL-10 could have an effect on innate and acquired immune responses to B. burgdorferi and influence the magnitude of the infectious inoculum and disease outcome. To understand the mechanism(s) of IL-10 action during early infection, when innate immunity expressed chiefly by skin macrophages is key, we investigated the effect of exogenous and endogenous IL-10 on the production of the macrophage-derived cytokines IL-6, IL-1beta, IL-12, and tumor necrosis factor alpha (TNF-alpha). We used the THP-1 human monocytic cell line and recombinant lipidated OspA (L-OspA) as the model target cell and stimulant, respectively. To determine the kinetics of cytokine production by THP-1 cells, we stimulated them with L-OspA and also with heat-killed B. burgdorferi cells (HBb) and lipopolysaccharide (LPS). Exogenous IL-10 dampened production of inflammatory cytokines, as elicited by lipoproteins. The inhibition of endogenous IL-10 function by anti-IL-10 antibody reduced the production of IL-12 and IL-6 but not that of IL-1beta and TNF-alpha. An inspection of the kinetics of cytokine production clarified this finding. TNF-alpha was produced prior to, and IL-beta was produced at the same time as, IL-10, whereas IL-6 and IL-12 were produced later. HBb, LPS, and L-OspA yielded similar kinetics of cytokine production. This result reinforces the notion that lipoproteins are the functional molecules in HBb and perhaps in vivo. It indicates also that signaling pathways utilized by LPS and lipoproteins may be extensively shared. The results are consistent with a major role played by IL-10 in controlling the initial phase of infection with this spirochete.

PMID: 11083779 [PubMed - indexed for MEDLINE]


15: J Immunol. 1999 Sep 1;163(5):2382-6.

Cutting edge: inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by toll-like receptor 2.

Hirschfeld M, Kirschning CJ, Schwandner R, Wesche H, Weis JH, Wooten RM, Weis JJ.

Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132, USA.

The agent of Lyme disease, Borrelia burgdorferi, produces membrane lipoproteins possessing potent inflammatory properties linked to disease pathology. The recent association of toll-like receptors (TLR) 2 and 4 with LPS responses prompted the examination of TLR involvement in lipoprotein signaling. The ability of human cell lines to respond to lipoproteins was correlated with the expression of TLR2. Transfection of TLR2 into cell lines conferred responsiveness to lipoproteins, lipopeptides, and sonicated B. burgdorferi, as measured by nuclear translocation of NF-kappaB and cytokine production. The physiological importance of this interaction was demonstrated by the 10-fold greater sensitivity of TLR2-transfected cells to lipoproteins than LPS. Futhermore, TLR2-dependent signaling by lipoproteins was facilitated by CD14. These data indicate that TLR2 facilitates the inflammatory events associated with Lyme arthritis. In addition, the widespread expression of lipoproteins by other bacterial species suggests that this interaction may have broad implications in microbial inflammation and pathogenesis.

PMID: 10452971 [PubMed - indexed for MEDLINE]


16: Infect Immun. 1999 Jan;67(1):140-7.

Induction of pro- and anti-inflammatory cytokines by Borrelia burgdorferi lipoproteins in monocytes is mediated by CD14.

Giambartolomei GH, Dennis VA, Lasater BL, Philipp MT.

Department of Parasitology, Tulane Regional Primate Research Center, Tulane University Medical Center, Covington, Louisiana 70433, USA.

We previously showed that heat-killed Borrelia burgdorferi spirochetes and lipidated outer surface protein A (L-OspA) stimulated the in vitro production of interleukin-10 (IL-10) in peripheral blood mononuclear cells (PBMC) from uninfected humans and rhesus monkeys (G. Giambartolomei et al., Infect. Immun. 66:2691-2697, 1998). Here we demonstrate that uninfected human peripheral blood monocytes, but not B or T cells, are the cells that transcribe the IL-10 cytokine gene in response to heat-killed B. burgdorferi. B. burgdorferi similarly induced an upregulation of the IL-1beta and IL-6 cytokine genes in monocytes and the production of IL-10 and IL-6 in culture supernatants of the human monocytic cell line THP-1. Purified L-OspA (but not unlipidated OspA [U-OspA] or U-OspC) also stimulated the production of both cytokines in THP-1 cells in a dose-dependent fashion, suggesting that acylation of the OspA protein molecule is required for the production of both anti- and pro-inflammatory cytokines in naive monocytes. A lipohexapeptide that contained the tripalmitoyl-modified cysteine motif (Pam3Cys-Hex) of B. burgdorferi lipoproteins but with an arbitrary peptide sequence had the same effect. Monoclonal antibodies (MAbs) MY4 and 60bca, both of which bind to CD14 and are known to block lipopolysaccharide (LPS)-mediated cytokine production, were able to block L-OspA-mediated IL-10 and IL-6 cytokine production. In contrast, MAb 26ic, which also binds to CD14 but does not block LPS function, failed to inhibit L-OspA-mediated cytokine production. These data suggest that activation of monocytes and production of both anti- and pro-inflammatory cytokines induced by lipoproteins proceeds via the CD14 receptor. LPS binding protein was not required for OspA-induced cytokine production. Our results demonstrate that pro- and anti-inflammatory cytokines induced by B. burgdorferi lipoproteins in PBMC are produced by monocytes and that lipoprotein and LPS signaling pathways share at least the initial signaling event that involves the CD14 receptor.

PMID: 9864208 [PubMed - indexed for MEDLINE]


6: Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7913-8. Epub 2003 Jun 10.

A newly discovered cholesteryl galactoside from Borrelia burgdorferi.

Ben-Menachem G, Kubler-Kielb J, Coxon B, Yergey A, Schneerson R.

Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. gilben@nih.gov

Two major glycolipids, which comprise approximately 36% of the total lipid mass from Borrelia burgdorferi, the etiological agent of Lyme disease, were investigated. We determined the fatty acid type, sugar identity, anomeric configuration, and substituent type and position. The structures were identified as cholesteryl 6-O-acyl-beta-d-galactopyranoside (B. burgdorferi glycolipid 1, BbGL-I), and 1,2-di-O-acyl-3-O-alpha-d-galactopyranosyl-sn-glycerol (BbGL-II). The major fatty acids were palmitate and oleate. The structures were corroborated by gas-liquid chromatography MS, matrix-assisted laser desorption/ionization time-of-flight spectroscopy, fast atom bombardment MS, detailed NMR spectrometry, and metabolic labeling. This is a previously undescribed demonstration of a cholesteryl galactoside in bacteria. Lipopolysaccharide was not detected in B. burgdorferi. The two glycolipids have several properties suggesting they may function as lipopolysaccharide: both are main components of the bacterial membrane, surface exposed, and have a three-domain structure. BbGL-I elicited specific antibodies in mice and rabbits, and BbGL-II elicited antibodies that reacted with both glycolipids.

PMID: 12799465 [PubMed - indexed for MEDLINE]


18: J Immunol. 1998 Jun 1;160(11):5485-92.

The role of CD14 in signaling mediated by outer membrane lipoproteins of Borrelia burgdorferi.

Wooten RM, Morrison TB, Weis JH, Wright SD, Thieringer R, Weis JJ.

Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132, USA.

Borrelia burgdorferi possesses membrane lipoproteins that exhibit stimulatory properties and, consequently, have been implicated in the pathology related to Lyme disease. As CD14 has been shown to mediate signaling by a number of lipid-modified bacterial products, the involvement of CD14 in signaling mediated by two B. burgdorferi lipoproteins, outer surface protein A (OspA) and OspC, was determined. Lipoprotein-mediated induction of nuclear factor-kappaB nuclear translocation and production of IL-8 and IL-6 in HUVEC was enhanced in the presence of serum or soluble rCD14. CD14-specific Abs that block LPS-mediated signaling also inhibited lipoprotein-dependent signaling in HUVEC and neutrophils. The formation of stable complexes between OspA and CD14 was demonstrated by native gel electrophoresis. LPS was found to compete with OspA for binding with CD14, suggesting that LPS and OspA bind similar regions on CD14. The similarity in binding was further supported by the finding that a mutant soluble CD14, lacking the LPS binding site, did not facilitate lipoprotein signaling, nor did it form a complex with OspA. Binding of OspA to CD14 was dependent on the lipid modification, as unlipidated OspA did not form a complex with CD14 or stimulate cells. In contrast, the lipopeptide remaining after proteinase K digestion both formed a complex with CD14 and retained stimulatory properties. These findings indicate that CD14 facilitates bacterial lipoprotein signaling in mammalian cells.

PMID: 9605151 [PubMed - indexed for MEDLINE]


39: Clin Sci. 1972 Sep;43(3):343-54.

Studies of the mechanism of the Jarisch-Herxheimer reaction in louse-borne relapsing fever: evidence for the presence of circulating Borrelia endotoxin.

Bryceson AD, Cooper KE, Warrell DA, Perine PL, Parry EH.

PMID: 5077513 [PubMed - indexed for MEDLINE]


21: J Immunol. 1997 May 15;158(10):4838-45.

Borrelia burgdorferi outer surface protein A (OspA) activates and primes human neutrophils.

Morrison TB, Weis JH, Weis JJ.

Department of Pathology, University of Utah Health Sciences Center, Salt Lake City 84132, USA.

Lyme disease is caused by infection with the spirochete Borrelia burgdorferi and is characterized by bacterial persistence and inflammation of many host tissues. B. burgdorferi express outer surface lipoproteins, including OspA, with inflammatory properties that could contribute to the localized tissue inflammation. Neutrophils are the predominant infiltrate into the inflamed arthritic joints, and are crucial for controlling the spirochete infection. They may also contribute to the joint pathology associated with Lyme arthritis. This study examines the effect of OspA on the activities of the neutrophil. Picomolar concentrations of OspA induce surface markers associated with neutrophil activation: increased CD10 and CD11b expression; decreased CD62-L expression; and an increased adherence to extracellular matrix. These events were similar in kinetics and magnitude to those induced by the strong activators LPS and FMLP. Like LPS, OspA could prime neutrophils for FMLP-induced release of lysosomal granules and production of superoxide. Thus, models of Lyme arthritis should include the possible contribution of direct activation of neutrophils to both defense and disease.

PMID: 9144499 [PubMed - indexed for MEDLINE]


23: Infect Immun. 1996 Sep;64(9):3845-52.

Activation of human monocytic cells by Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides proceeds via a pathway distinct from that of lipopolysaccharide but involves the transcriptional activator NF-kappa B.

Norgard MV, Arndt LL, Akins DR, Curetty LL, Harrich DA, Radolf JD.

Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235, USA.

There is increasing evidence that lipoproteins of Treponema pallidum and Borrelia burgdorferi are key inflammatory mediators during syphilis and Lyme disease. A principal objective of the present study was to identify more precisely similarities and divergences among lipopolysaccharide (LPS)- and lipoprotein-lipopeptide-induced immune cell signaling events. Like LPS, purified native B. burgdorferi OspA and synthetic analogs of OspA, OspB, and two T. pallidum lipoproteins (Tpp47 and Tpp17) all induced NF-kappa B translocation in THP-1 human monocytoid cells. Acylation of OspA and the synthetic peptides was requisite for cell activation. Polymyxin B abrogated only the response to LPS. By using 70Z/3-derived pre-B-cell lines either lacking or expressing human CD14 (the LPS receptor), it was observed that expression of human CD14 imparted responsiveness to LPS but not to OspA or spirochetal lipopeptides (assessed by induction of NF-kappa B and expression of surface immunoglobulin M). Finally, the biological relevance of the observation that T. pallidum lipoproteins-lipopeptides induce both NF-kappa B and cytokine production in monocytes was supported by the ability of the synthetic analogs to promote human immunodeficiency virus replication in chronically infected U1 monocytoid cells; these observations also suggest a potential mechanism whereby a syphilitic chancre can serve as a cofactor for human immunodeficiency virus transmission. The combined data lend additional support to the proposal that spirochetal lipoproteins and LPS initiate monocyte activation via different cell surface events but that the signaling pathways ultimately converge to produce qualitatively similar cellular responses.

PMID: 8751937 [PubMed - indexed for MEDLINE]


25: Immunology. 1994 Jul;82(3):389-96.

A 14,000 MW lipoprotein and a glycolipid-like structure of Borrelia burgdorferi induce proliferation and immunoglobulin production in mouse B cells at high frequencies.

Honarvar N, Schaible UE, Galanos C, Wallich R, Simon MM.

Max-Planck-Institut fur Immunbiologie, Freiburg, Germany.

Sonicated preparations of Borrelia burgdorferi are able to stimulate unselected resting BALB/c spleen cells to proliferate and to produce immunoglobulin in vitro. FACS analysis of target cells prestained with an integrated cell-surface marker as well as cell-depletion experiments demonstrate that the majority of responding lymphocytes are B cells. Limiting dilution analyses of resting B cells revealed high frequencies of cells producing IgM (F 1/11-1/62) or IgG (F 1/5-1/163) in response to B. burgdorferi sonicate (B.b. sonicate). These numbers were similar to those obtained with lipopolysaccharide (LPS) (IgM: F 1/20-1/84; IgG: F 1/14-1/85) or a synthetic lipopeptide of Braun's Escherichia coli lipoprotein (IgM: F 1/15, 1/19; IgG: F 1/148, 1/34). The mitogenic structure(s) expressed by B. burgdorferi is distinct from LPS, as similar proliferative responses were obtained with B cells from LPS-resistant (C57BL/10ScCr and C3H/HeJ) and LPS-susceptible (C57BL/10ScSn, C3H/HeN) mice.

Furthermore, B-cell mitogenic properties were also found in two distinct fractions of a phenol-chloroform-petroleum ether extract of B. burgdorferi: they consisted of a lipoprotein distinct from the outer surface proteins (Osp) A and B and glycolipid-like structures, respectively. These data suggest that spirochetes express a multitude of distinct structures with mitogenic activity for B cells including various lipoproteins as well as glycolipid(s).

PMID: 7959873 [PubMed - indexed for MEDLINE]


28: FASEB J. 1992 Apr;6(7):2482-6.

Interleukin-1 (IL-1) receptor blockade reduces endotoxin and Borrelia burgdorferi-stimulated IL-8 synthesis in human mononuclear cells.

Porat R, Poutsiaka DD, Miller LC, Granowitz EV, Dinarello CA.

Department of Medicine, New England Medical Center, Boston, Massachusetts 02111.

Interleukin-1 (IL-1) is a potent stimulator of IL-8 production by fibroblasts and monocytes. In the present study, we asked how much of endotoxin (LPS)-induced IL-8 production by human peripheral blood mononuclear cells was due to IL-1 induced by LPS. Cells were stimulated with either IL-1 beta, LPS, or Borrelia burgdorferi, and total IL-8 was determined by a specific radioimmunoassay. The addition of saturating concentrations of IL-1 receptor antagonist protein (IRAP) reduced the IL-1 beta-, LPS-, and B. burgdorferi-induced IL-8 synthesis by 85, 50, and 40%, respectively. Increasing the concentration of LPS did not affect the reduction in IL-8 synthesis observed in the presence of IRAP. Significant inhibition of the IL-1 beta-induced IL-8 synthesis was observed when IRAP was added 60 or 90 min after IL-1 beta; similarly, IL-8 synthesis after LPS was also reduced by delayed addition of IRAP. These data suggest that the ameliorative effects of IL-1 receptor blockade in models of inflammation and infection may be due, in part, to suppression of IL-1-induced IL-8.

PMID: 1532945 [PubMed - indexed for MEDLINE]


30: J Infect Dis. 1992 Mar;165(3):471-8.

Comment in: J Infect Dis. 1992 Oct;166(4):938-9.

Nonspecific proliferative responses of murine lymphocytes to Borrelia burgdorferi antigens.

de Souza MS, Fikrig E, Smith AL, Flavell RA, Barthold SW.

Section of Comparative Medicine; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510.

Proliferative responses of naive splenocytes to Borrelia burgdorferi antigens from mice susceptible (C3H) and resistant (BALB) to Lyme borreliosis were investigated. B. burgdorferi spirochetes and recombinant outer surface proteins, OspA and OspB, were found to induce nonspecific proliferation of naive splenocytes from both strains of mice. Cell purification studies localized nonspecific proliferation to the B cell-enriched fraction. B. burgdorferi, OspA, and OspB were found to induce IgM and IgG synthesis in vitro. The mitogenic effect of B. burgdorferi was dissimilar to that of lipopolysaccharide (LPS), in that B cells from C3H/HeJ mice (LPS-unresponsive) responded at levels comparable to those from C3H/HeNCrlBr mice. These results emphasize the need for caution in the study of antigen-specific proliferation for B. burgdorferi.

PMID: 1531672 [PubMed - indexed for MEDLINE]


38: Zentralbl Bakteriol Mikrobiol Hyg [A]. 1986 Dec;263(1-2):137-41

Borrelia burgdorferi lipopolysaccharide and its role in the pathogenesis of Lyme disease.

Habicht GS, Beck G, Benach JL, Coleman JL.

Lipopolysaccharides (LPS) are a constitutive part of the outer wall of gram negative bacteria. Because many of the symptoms of Lyme disease could be explained by a spirochetal LPS we have subjected Borrelia burgdorferi to standard LPS extraction techniques which yielded a LPS which accounted for 1.5-4% of the dry weight. The LPS was very similar to classical gram negative bacterial LPS both chemically and in its biological activities which included pyrogenicity, mitogenicity for lymphocytes and the induction of Interleukin 1 production by macrophages. In addition, the LPS produced an acute inflammatory reaction when injected intradermally into rabbit skin. It could also prepare a skin site for the production of the local Shwartzman reaction. These results show that the Lyme disease spirochete contains a hitherto unknown LPS that is biologically active in vitro and in vivo. It is likely that this molecule plays an important role in the pathogenesis of Lyme disease.

PMID: 3577475 [PubMed - indexed for MEDLINE]


40: Microbiologica. 1986 Apr;9(2):249-52.

Endotoxicity associated with the Lyme disease Borrelia: recent findings.

Fumarola D, Munno I, Marcuccio C, Miragliotta G.

The endotoxicity of Borrelia burgdorferi, the causative agent of Lyme Disease, a tick-borne spirochetosis, was studied using Limulus assay and pyrogen test in rabbit. Some suspensions of Ixodes ricinus and Ixodes dammini associated Borrelia were able to gelify Limulus lysate and demonstrated a febrile response in rabbit. These findings and other recent data demonstrating an endotoxin-like activity of the Lyme Disease agent are discussed in the context of the pathogenic mechanisms of the illness.

PMID: 3713546 [PubMed - indexed for MEDLINE]


42: Infection. 1983 Nov-Dec;11(6):345.

"Endotoxicity" of the Lyme disease spirochete.

Fumarola D, Munno I, Miragliotta G.

Publication Types: Letter

PMID: 6668073 [PubMed - indexed for MEDLINE]


8: Vaccine. 1997 Jun;15(9):988-96.

OspA lipoprotein of Borrelia burgdorferi is a mucosal immunogen and adjuvant.

Erdile LF, Guy B.

Pasteur Merieux Connaught, Marcy L'Etoile, France.

The outer surface protein A (OspA) lipoprotein of Borrelia burgdorferi, like cholera toxin and the heat-labile enterotoxin of Escherichia coli, induces pro-inflammatory cytokines. This suggested that, like those toxins, OspA might be a mucosal immunogen and adjuvant. OspA, administered intranasally (i.n.) or intragastrically, induced strong serum IgG and salivary gland IgA responses. The serum IgG isotypes were indicative of a mixed T helper 1 and T helper 2 response, the latter being more pronounced. The N-terminal tripalmitoyl-S-glyceryl-cysteine (Pam3Cys) lipid moiety was absolutely required. OspA strongly enhanced the serum IgG and salivary gland IgA responses to jack bean urease co-administered by the i.n. route. OspA also enhanced the response to tetanus toxoid and induced limited protection against challenge. A synthetic lipopeptide also adjuvanted the response to urease by the i.n. route, but was ca 500-fold less potent on a molar basis than OspA. These results suggest that OspA or other lipoproteins may be useful in mucosal vaccines.

PMID: 9261945 [PubMed - indexed for MEDLINE]


Immunology. 2004 Nov;113(3):401-8.

Characterization of the B-cell inhibitory protein factor in Ixodes ricinus tick saliva: a potential role in enhanced Borrelia burgdoferi transmission.

Hannier S, Liversidge J, Sternberg JM, Bowman AS.

School of Biological Science, Zoology, University of Aberdeen, UK.

We recently described the inhibition of host B lymphocytes by Ixodes ricinus tick saliva. In this study, we characterized the factor responsible for this activity and examined the modulation of lipopolysaccharide (LPS)- and Borrelia burgdorferi outer surface protein (Osp)-induced proliferation of naive murine B lymphocytes by an enriched fraction of this factor. The B-lymphocyte inhibitory activity was destroyed by trypsin treatment, indicating that a proteinaceous factor was responsible for this activity. The removal of glutathione-S-transferase (GST) from tick salivary glands extracts (SGE) showed that this B-cell inhibitory protein (BIP) was not a GST. Gel filtration liquid chromatography indicated that BIP has a native molecular weight of approximately 18,000. An enrichment protocol, using a combination of anion-exchange and reverse-phase liquid chromatography, was established. BIP-enriched fractions did not suppress T-cell proliferation. Delayed addition of BIP-enriched fractions, up to 7 hr after LPS addition, inhibited the proliferation of isolated B cells. BIP-enriched fractions dramatically inhibited both OspA- and OspC-induced proliferation of isolated B cells. These results strongly suggest that BIP may facilitate B. burgdorferi transmission by preventing B-cell activation, and also highlights the potential of BIP as a therapeutic agent in B-cell maladies.

PMID: 15500628 [PubMed - indexed for MEDLINE]


25: Microbiologica. 1986 Apr;9(2):249-52.

Endotoxicity associated with the Lyme disease Borrelia: recent findings.

Fumarola D, Munno I, Marcuccio C, Miragliotta G.

The endotoxicity of Borrelia burgdorferi, the causative agent of Lyme Disease, a tick-borne spirochetosis, was studied using Limulus assay and pyrogen test in rabbit. Some suspensions of Ixodes ricinus and Ixodes dammini associated Borrelia were able to gelify Limulus lysate and demonstrated a febrile response in rabbit. These findings and other recent data demonstrating an endotoxin-like activity of the Lyme Disease agent are discussed in the context of the pathogenic mechanisms of the illness.

PMID: 3713546 [PubMed - indexed for MEDLINE]


2: Arthritis Rheum. 2004 Jul;50(7):2360-9.

Outer surface lipoproteins of Borrelia burgdorferi vary in their ability to induce experimental joint injury.

Batsford S, Dunn J, Mihatsch M.

Albert Ludwigs University, Freiburg, Germany. bats@ukl.uni-freiburg.de

OBJECTIVE: To examine the ability of bacterial lipoproteins from the spirochete Borrelia burgdorferi to cause in vivo tissue injury (arthritis). METHODS: Outer surface proteins (OSPs) from B burgdorferi were used in a rat model of antigen-induced allergic arthritis. Intraarticular challenge with recombinant OspA, OspB, and OspC in nonlipidated (peptide) and lipidated forms was performed in the left knee joint; the contralateral joint received buffer as control. Inflammation was monitored by technetium scintigraphy and histology. RESULTS: Nonlipidated (peptide) OspA, OspB, and OspC did not induce arthritis; the only exception was polymerized OspA, which was tested in preimmunized rats. Lipidated OspA from 2 different strains and lipidated OspC induced severe arthritis, whereas lipidated OspB failed to induce injury. A synthetic analog of the OSP lipid modification, lipopeptide Pam(3)Cys-Ser-Lys(4)-OH, either alone or coupled to bovine serum albumin, also failed to induce injury. Injury did not develop in control groups that were given the appropriate buffers or lipopolysaccharide. This showed that lipidated borrelial OSPs can be potent arthritogens, but vary greatly with respect to their injury-inducing potential. The possession of a lipid modification is essential but is not sufficient to render an OSP arthritogenic. CONCLUSION: This is the first study to demonstrate that individual lipoproteins from B burgdorferi can induce experimental joint injury in vivo. These results may help elucidate the pathogenesis of Lyme arthritis and, above all, underline the importance of bacterial lipoproteins as major virulence factors.

PMID: 15248237 [PubMed - indexed for MEDLINE]


4: Infect Immun. 2003 Jul;71(7):3979-87.

Borrelia burgdorferi-induced tolerance as a model of persistence via immunosuppression.

Diterich I, Rauter C, Kirschning CJ, Hartung T.

Biochemical Pharmacology, Faculty of Biology, University of Konstanz, Konstanz, Germany.

If left untreated, infection with Borrelia burgdorferi sensu lato may lead to chronic Lyme borreliosis. It is still unknown how this pathogen manages to persist in the host in the presence of competent immune cells. It was recently reported that Borrelia suppresses the host's immune response, thus perhaps preventing the elimination of the pathogen (I. Diterich, L. Harter, D. Hassler, A. Wendel, and T. Hartung, Infect. Immun. 69:687-694, 2001). Here, we further characterize Borrelia-induced immunomodulation in order to develop a model of this anergy. We observed that the different Borrelia preparations that we tested, i.e., live, heat-inactivated, and sonicated Borrelia, could desensitize human blood monocytes, as shown by attenuated cytokine release upon restimulation with any of the different preparations. Next, we investigated whether these Borrelia-specific stimuli render monocytes tolerant, i.e. hyporesponsive, towards another Toll-like receptor 2 (TLR2) agonist, such as lipoteichoic acid from gram-positive bacteria, or towards the TLR4 agonist lipopolysaccharide. Cross-tolerance towards all tested stimuli was induced. Furthermore, using primary bone marrow cells from TLR2-deficient mice and from mice with a nonfunctional TLR4 (strain C3H/HeJ), we demonstrated that the TLR2 was required for tolerance induction by Borrelia, and using neutralizing antibodies, we identified interleukin-10 as the key mediator involved. Although peripheral blood mononuclear cells tolerized by Borrelia exhibited reduced TLR2 and TLR4 mRNA levels, the expression of the respective proteins on monocytes was not decreased, ruling out the possibility that tolerance to Borrelia is attributed to a reduced TLR2 expression. In summary, we characterized tolerance induced by B. burgdorferi, describing a model of desensitization which might mirror the immunosuppression recently attributed to the persistence of Borrelia in immunocompetent hosts.

PMID: 12819085 [PubMed - indexed for MEDLINE]


5: Dtsch Med Wochenschr. 2003 Mar 7;128(10):513.

[What is to be made of the therapy of borreliosis with cholestyramine and pioglitazone?]

[Article in German]

Hassler D.

PMID: 12627347 [PubMed - indexed for MEDLINE]


11: Semin Neurol. 1994 Dec;14(4):313-9.

Central nervous system vasculitis secondary to infections, toxins, and neoplasms.

Giang DW.

Department of Neurology, University of Rochester Medical Center, New York, USA.

Publication Types: Review

PMID: 7709082 [PubMed - indexed for MEDLINE]


12: Infect Immun. 1992 Aug;60(8):3224-30.

Hemolytic activity of Borrelia burgdorferi.

Williams LR, Austin FE.

Department of Microbiology and Immunology, School of Medicine, University of Louisville, Kentucky 40292.

Zones of beta-hemolysis occurred around colonies of Borrelia burgdorferi grown on Barbour-Stoenner-Kelly medium containing agarose and horse blood. Blood plates were inoculated with either the infective strain Sh-2-82 or noninfective strain B-31 in an overlay and incubated in a candle jar. Both strains of B. burgdorferi displayed beta-hemolysis after 1 to 2 weeks of incubation. The hemolytic activity diffused out from the borrelial colonies, eventually resulting in lysis of the entire blood plate. Hemolysis was most pronounced with horse blood and was less intense with bovine, sheep, and rabbit blood. Hemolysis was enhanced by hot-cold incubation, which is typical of phospholipase-like activities in other bacteria. Further characterization of the borrelial hemolysin by using a spectrophotometric assay revealed its presence in the supernatant fluids of stationary-phase cultures. Detection of the borrelial hemolytic activity was dependent on activation of the hemolysin by the reducing agent cysteine. This study provides the first evidence of hemolytic activity associated with B. burgdorferi.

PMID: 1639493 [PubMed - indexed for MEDLINE]


13: Infect Immun. 1992 Mar;60(3):1109-13.

In vitro and in vivo induction of tumor necrosis factor alpha by Borrelia burgdorferi.

Defosse DL, Johnson RC.

Department of Microbiology, University of Minnesota, Minneapolis 55455.

Tumor necrosis factor alpha (TNF-alpha) is an immunoregulatory cytokine with many biological activities including the mediation of inflammation. We examined sera and synovial fluids from patients seropositive for infection with Borrelia burgdorferi using a radioimmunoassay specific for TNF-alpha. Significant elevation of TNF-alpha was found in the sera and synovial fluids of patients examined, while controls showed no elevation. Sera of mice infected with B. burgdorferi contained elevated levels of TNF-alpha which varied during the course of a 24-day infection. To determine whether B. burgdorferi is capable of inducing TNF-alpha production, spirochetes were added to adherent human peripheral blood mononuclear cells or mouse peritoneal exudate cells and 24 h later supernatants were assayed. TNF-alpha induction occurred in a dose-dependent manner. The maximum stimulation occurred when a ratio of 1 to 10 spirochetes per mononuclear cell was used. At optimal concentrations, induction was not diminished by inactivation of spirochetes or pretreatment with polymyxin B. These results suggest that an increase in TNF-alpha production may occur as a result of infection with B. burgdorferi.

PMID: 1541526 [PubMed - indexed for MEDLINE]


14: J Infect Dis. 1992 Mar;165(3):471-8.

Comment in: J Infect Dis. 1992 Oct;166(4):938-9.

Nonspecific proliferative responses of murine lymphocytes to Borrelia burgdorferi antigens.

de Souza MS, Fikrig E, Smith AL, Flavell RA, Barthold SW.

Section of Comparative Medicine; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510.

Proliferative responses of naive splenocytes to Borrelia burgdorferi antigens from mice susceptible (C3H) and resistant (BALB) to Lyme borreliosis were investigated. B. burgdorferi spirochetes and recombinant outer surface proteins, OspA and OspB, were found to induce nonspecific proliferation of naive splenocytes from both strains of mice. Cell purification studies localized nonspecific proliferation to the B cell-enriched fraction. B. burgdorferi, OspA, and OspB were found to induce IgM and IgG synthesis in vitro. The mitogenic effect of B. burgdorferi was dissimilar to that of lipopolysaccharide (LPS), in that B cells from C3H/HeJ mice (LPS-unresponsive) responded at levels comparable to those from C3H/HeNCrlBr mice. These results emphasize the need for caution in the study of antigen-specific proliferation for B. burgdorferi.

PMID: 1531672 [PubMed - indexed for MEDLINE]


15: J Infect Dis. 1991 Sep;164(3):568-74.

Cytokines and the pathogenesis of neuroborreliosis: Borrelia burgdorferi induces glioma cells to secrete interleukin-6.

Habicht GS, Katona LI, Benach JL.

Department of Pathology, State University of New York, Stony Brook 11794-8691.

Lyme disease is a multisystemic disease caused by a tickborne spirochete, Borrelia burgdorferi. Neuroborreliosis is characterized by intrathecal production of antibodies specific for the spirochete. This suggests that spirochetal infection of the central nervous system produces conditions that support the maturation of B lymphocytes to immunoglobulin-secreting cells. Interleukin 6 (IL-6) stimulates B cell differentiation into antibody-secreting cells. The present study was undertaken to determine whether B. burgdorferi can stimulate cells of central nervous system origin to secrete IL-6. C6 rat glioma cells cultured with spirochetes induced secretion of IL-6 activity. Peak stimulation was achieved at 24 h with 25 spirochetes per glioma cell. Glioma cells were also stimulated to produce IL-6 by interleukin 1 and tumor necrosis factor. That very few spirochetes are found in Lyme disease patients suggests that biologic amplification factors derived from the organism or the host, or both, are responsible for the pathogenesis of this disease. IL-6 can now be added to the growing list of such factors.

PMID: 1908002 [PubMed - indexed for MEDLINE]


16: Rev Infect Dis. 1991 Jul-Aug;13(4):658-65.

Plagues--what's past is present: thoughts on the origin and history of new infectious diseases.

Ampel NM.

Medical Service, Tucson Veterans Affairs Medical Center, Arizona 85723.

Medical science has made tremendous strides in overcoming infectious diseases in the 20th century. Despite this, several epidemics of previously unrecognized diseases have occurred during the last 15 years. These diseases include Lyme disease, Legionnaires' disease, toxic shock syndrome, and AIDS. Examination of past epidemics, including the plague of Athens, the black death, syphilis, and influenza, suggests that the sudden occurrence of diseases that were previously unrecognized is not unusual. Analysis of the new infectious disease indicates that while all four appeared suddenly, isolated cases of the disease occurred before the actual epidemic. Further, all four new diseases were found to be due to agents or toxins that were not previously recognized. Epidemics due to new infectious diseases may arise by several mechanisms, including mutation of the pathogen to a virulent form and introduction of an infectious agent into a nonimmune population. Environmental and behavioral factors may play an important role, as illustrated by toxic shock syndrome, Legionnaires' disease, and AIDS. On the other hand, epidemic diseases tend to abate over time because of changes in the infecting pathogen and in the host. Hence, epidemics can be seen as cycles; new diseases will arise periodically, occasionally with a devastating outcome. With time the effects of these diseases on the population will ameliorate. The cycle will begin again when a new disease emerges.

Publication Types: Review; Review, Tutorial

PMID: 1925288 [PubMed - indexed for MEDLINE]


17: FEMS Microbiol Immunol. 1991 Feb;3(1):33-8. Related Articles, Links

Evidence for (lipo) oligosaccharides in Borrelia burgdorferi and their serological specificity.

Cinco M, Banfi E, Balanzin D, Godeas C, Panfili E.

Istituto di Microbiologia, Universita degli Studi, Trieste, Italy.

SDS-PAGE and Western immunoblot profiles have been determined for different strains of Borrelia burgdorferi. Major proteins of 60 kDa, 41 kDa corresponding to flagellin, 34-36 kDa and 30-31 kDa corresponding to OspB and OspA respectively, and 18-20 kDa corresponding to 'pC' fractions were detected. A "rough" lipopolysaccharide which we called lipooligosaccharide (LOS) of 8-11 kDa appeared to be present, being detected by specific silver staining, as in crude Borrelia lysates as in proteinase K digested Borrelia strains, quite similar in shape among the different strains examined. The LOS reacted in Western blotting with immune anti-B. burgdorferi rabbit serum and also with sera collected from humans affected by Lyme borreliosis. The LOS did not react with sera positive for syphilis or leptospirosis, and their immunological specificity is discussed.

PMID: 1711876 [PubMed - indexed for MEDLINE]


19: Ann N Y Acad Sci. 1988;539:80-6.

The role of interleukin-1 in the pathogenesis of Lyme disease.

Habicht GS, Beck G, Benach JL.

Department of Pathology, State University of New York, Stony Brook 11794.

PMID: 3263828 [PubMed - indexed for MEDLINE]


21: Sci Am. 1987 Jul;257(1):78-83.

Lyme disease.

Habicht GS, Beck G, Benach JL.

PMID: 3496660 [PubMed - indexed for MEDLINE]


25: Microbiologica. 1986 Apr;9(2):249-52.

Endotoxicity associated with the Lyme disease Borrelia: recent findings.

Fumarola D, Munno I, Marcuccio C, Miragliotta G.

The endotoxicity of Borrelia burgdorferi, the causative agent of Lyme Disease, a tick-borne spirochetosis, was studied using Limulus assay and pyrogen test in rabbit. Some suspensions of Ixodes ricinus and Ixodes dammini associated Borrelia were able to gelify Limulus lysate and demonstrated a febrile response in rabbit. These findings and other recent data demonstrating an endotoxin-like activity of the Lyme Disease agent are discussed in the context of the pathogenic mechanisms of the illness.

PMID: 3713546 [PubMed - indexed for MEDLINE]


26: Eur J Clin Microbiol. 1985 Aug;4(4):440.

Lyme arthritis: does endotoxin play a role?

Fumarola D, Munno I, Miragliotta G, Marcuccio C.

Publication Types: Letter

PMID: 4043072 [PubMed - indexed for MEDLINE]


27: J Infect Dis. 1985 Jul;152(1):108-17.

Chemical and biologic characterization of a lipopolysaccharide extracted from the Lyme disease spirochete (Borrelia burgdorferi).

Beck G, Habicht GS, Benach JL, Coleman JL.

A lipopolysaccharide (LPS) was isolated from the Lyme disease spirochete by a modification of the hot phenol-water method. The material was composed of 45% carbohydrate, 8% protein, 44% lipid A, and 1% 3-deoxy-D-mannooctulosonic acid and accounted for approximately 1.5% of the cellular dry weight. The isolated LPS possessed several biologic activities characteristic of endotoxins. The LPS was pyrogenic for rabbits, mitogenic for human mononuclear cells and murine splenocytes, capable of clotting limulus lysate, and cytotoxic for murine macrophages. LPS extracted from Borrelia burgdorferi by the petroleum-ether:chloroform:liquid-phenol procedure was also characterized. The results show that the Lyme disease spirochete contains a hitherto unknown LPS that is biologically active in vitro, and the expression of such activities in vivo may play an important role in the pathogenesis of Lyme disease. Some of the clinical manifestations of other spirochetal disease may be explained by similar endotoxins in those organisms. To our knowledge this is the first report of an LPS extracted from a spirochete that is known to be a human pathogen.

PMID: 4008983 [PubMed - indexed for MEDLINE]


29: Ann Intern Med. 1985 Mar;102(3):397-9.

Relapsing fever: new lessons about antibiotic action.

Butler TC.

PMID: 3970476 [PubMed - indexed for MEDLINE]


30: J Infect Dis. 1984 Oct;150(4):616.

Failure to detect endotoxin in sera from patients with Lyme disease.

Schmid GP, Verardo L, Highsmith AK, Weisfeld JS.

Publication Types: Letter

PMID: 6491371 [PubMed - indexed for MEDLINE]


32: Lancet. 1983 Apr 16;1(8329):835-9.

Meptazinol diminishes the Jarisch-Herxheimer reaction of relapsing fever.

Teklu B, Habte-Michael A, Warrell DA, White NJ, Wright DJ.

Naloxone, an opioid antagonist, and meptazinol, an opioid antagonist with agonist properties, were tested in a double-blind placebo-controlled trial in 24 Ethiopian patients with louse-borne relapsing fever. The potentially fatal Jarisch-Herxheimer reaction (J-HR), which invariably follows tetracycline treatment of the disease, was unaffected by naloxone, 30-40 mg intravenously, but was diminished by meptazinol, 300-500 mg intravenously. Compared with naloxone and placebo, meptazinol reduced the clinical severity of the reaction, significantly delayed and shortened its chill phase, delayed the rise in temperature, and reduced peak temperature and changes in pulse and respiratory rates and leucocyte count. High-dose corticosteroids given before or at the time of tetracycline treatment failed to alter the reaction, which is thought to result from release of endotoxin-like substances. Meptazinol is the first effective treatment for the J-HR of louse-borne relapsing fever. This finding suggests a role for endogenous opioids in the pathogenesis of the J-HR.

Publication Types: Clinical Trial; Randomized Controlled Trial

PMID: 6132178 [PubMed - indexed for MEDLINE]


34: Parasite Immunol. 1980 Autumn;2(3):201-21.

Reaction following treatment of murine borreliosis and Shwartzman type reacion with borrelial sonicates.

Wright DJ.

Treatment of experimental murine borreliosis induced an acute transient fall in temperature, leucopenia and thrombocytopenia with appearance of circulating 'endotoxin-like' material. This reaction to treatment could be reproduced by the inoculatioh of borrelial sonicates into infected mice or by two injections of the same sonicate given 24 hours apart, into normal mice. Sensitization or precipitation of the reaction could not be induced by E. coli lipopolysaccharide, although a reaction indistinguishable from the reaction to treatment could be provoked in mice by two successive injections of lipopolysaccharide given 24 hours apart. The nature of this reaction in mice was investigated and the relation of both reactions to the Shwartzman reaction, Endotoxin.

PMID: 7413246 [PubMed - indexed for MEDLINE]


37: Am J Med. 1977 Dec;63(6):933-8.

Activation of protein mediators of inflammation and evidence for endotoxemia in Borrelia recurrentis infection.

Galloway RE, Levin J, Butler T, Naff GB, Goldsmith GH, Saito H, Awoke S, Wallace CK.

Fifteen patients with Borrelia recurrentis infection were studied to evaluate the role of certain plasma proteins and endotoxin in the pathophysiology of both the acute illness and the Jarisch-Herxheimer-like reaction. The causative spirochetes disappeared from the blood during the Jarisch-Herxheimer-like reaction, which occurred about 2 hours after antibiotic therapy. The mean titers of Hageman factor, plasma prekallikrein and serum hemolytic complement activity were decreased at the time of admission and 2 hours after treatment, and rose to normal values during convalescence. Serum properdin titers were decreased in 14 patients at the time of admission, in 12 patients 2 hours after treatment, and in none during convalescence. The frequency of elevated levels of fibrinogen-related antigens increased from three patients at the time of admission to 12 patients 2 hours after treatment. Results of plasma limulus tests for endotoxin-like material were positive in 11 patients at the time of admission and in 13 patients 2 hours after treatment. These findings demonstrated that Hageman factor, prekallikrein and proteins of the complement system are activated in B. recurrentis infection and that endotoxin may play a role in both the acute illness and in the development of the Jarisch-Herxheimer-like reaction after treatment.

PMID: 605915 [PubMed - indexed for MEDLINE]


38: J Infect Dis. 1976 Jun;133(6):696-704.

Clinical pathology of the Jarisch-Herxheimer reaction.

Bryceson AD.

The Jarisch-Herxheimer reaction is a complication that can follow treatment of several infectious diseases. Its most severe form is in louse-borne relapsing fever; in this syndrome the reaction can cause death. Information from studies in Ethiopia during the past eight years is presented, and clinical, physiological, pathological, and immunological features of the reaction are described. Possible causative mechanisms of the reaction are discussed, especially in relation to the role of endotoxin, and an attempt is made to consider this reaction in relation to other endotoxin-associated states.

PMID: 932495 [PubMed - indexed for MEDLINE]


The quote in the introduction from Dr. James Howenstine is from: http://69.93.158.250/forums/m.asp?f=58&i=444

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