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Helminth infection induces resistin

Discussion in 'Alternative Therapies' started by jaybee00, Dec 8, 2017.

  1. jaybee00

    jaybee00 Senior Member

    Interesting because Montoya found low resistin levels in PWCFS. Which labs can test for resistin? Thanks.
    Human resistin protects against endotoxic shock by blocking LPS–TLR4 interaction

    Jessica C. Janga,1,
    Author Affiliations

    1. Edited by Genhong Cheng, University of California, Los Angeles, CA, and accepted by Editorial Board Member Tadatsugu Taniguchi October 20, 2017 (received for review September 12, 2017)
    1. Abstract
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    Gram-negative bacterial sepsis is a life-threatening disease that is exacerbated by an uncontrolled immune response to the endotoxin lipopolysaccharide (LPS). Human resistin is a highly expressed cytokine in sepsis, where it is hypothesized to exacerbate inflammation. We identify an unexpected protective role for resistin in endotoxic shock. We use human resistin-expressing transgenic mice and human immune cell assays to show that resistin prevents LPS-induced mortality by blocking LPS binding to its receptor Toll-like receptor 4 (TLR4) and by promoting anti-inflammatory signaling. Helminth infection-induced resistin and treatment with recombinant resistin or resistin N-terminal peptides also inhibited LPS function. These studies report a protective function for resistin and identify the therapeutic potential of resistin-mediated anti-inflammatory pathways or resistin-based reagents in sepsis.

    Helminths trigger multiple immunomodulatory pathways that can protect from sepsis. Human resistin (hRetn) is an immune cell-derived protein that is highly elevated in helminth infection and sepsis. However, the function of hRetn in sepsis, or whether hRetn influences helminth protection against sepsis, is unknown. Employing hRetn-expressing transgenic mice (hRETNTg+) and recombinant hRetn, we identify a therapeutic function for hRetn in lipopolysaccharide (LPS)-induced septic shock. hRetn promoted helminth-induced immunomodulation, with increased survival of Nippostrongylus brasiliensis (Nb)-infected hRETNTg+ mice after a fatal LPS dose compared with naive mice or Nb-infected hRETNTg− mice. Employing immunoprecipitation assays, hRETNTg+Tlr4−/− mice, and human immune cell culture, we demonstrate that hRetn binds the LPS receptor Toll-like receptor 4 (TLR4) through its N terminal and modulates STAT3 and TBK1 signaling, triggering a switch from proinflammatory to anti-inflammatory responses. Further, we generate hRetn N-terminal peptides that are able to block LPS proinflammatory function. Together, our studies identify a critical role for hRetn in blocking LPS function with important clinical significance in helminth-induced immunomodulation and sepsis.

    cigana, Hip, Art Vandelay and 2 others like this.
  2. Hip

    Hip Senior Member

    This may be of relevance on the thread: Incredible improvements with Helminthic Therapy where one severe bedbound ME/CFS patient was able to get back to work as a result of helminth therapy.

    Resistin appears to be induced by helminth infection, and resistin can be pro-inflammatory in some contexts (this study says that helminth infection causes the release of resistin, which then promotes proinflammatory cytokines and impedes parasite clearance).

    However, in the study you quoted above, resistin seems to have anti-inflammatory effects, by blocking the LPS-induced activation of TLR-4.

    This then perhaps makes helminth therapy for ME/CFS similar to low-dose naltrexone (LDN) therapy, as LDN
    blocks TLR-4 on microglia (among other things: LDN also increases levels of met-enkephalin and blocks the mu-opioid, delta-opioid and kappa-opioid receptors).
    cigana and sb4 like this.

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