Therapeutic effects of treatment with anti-TLR2 and anti-TLR4 monoclonal antibodies in polymicrobial sepsis
PloS one, 2015•journals.plos.org
Introduction Toll-like receptors (TLRs) play an important role in the recognition of microbial
products and in host defense against infection. However, the massive release of
inflammatory mediators into the bloodstream following TLR activation following sepsis is
thought to contribute to disease pathogenesis. Methods Here, we evaluated the effects of
preventive or therapeutic administration of monoclonal antibodies (mAbs) targeting either
TLR2 or TLR4 in a model of severe polymicrobial sepsis induced by cecal ligation and …
products and in host defense against infection. However, the massive release of
inflammatory mediators into the bloodstream following TLR activation following sepsis is
thought to contribute to disease pathogenesis. Methods Here, we evaluated the effects of
preventive or therapeutic administration of monoclonal antibodies (mAbs) targeting either
TLR2 or TLR4 in a model of severe polymicrobial sepsis induced by cecal ligation and …
Introduction
Toll-like receptors (TLRs) play an important role in the recognition of microbial products and in host defense against infection. However, the massive release of inflammatory mediators into the bloodstream following TLR activation following sepsis is thought to contribute to disease pathogenesis.
Methods
Here, we evaluated the effects of preventive or therapeutic administration of monoclonal antibodies (mAbs) targeting either TLR2 or TLR4 in a model of severe polymicrobial sepsis induced by cecal ligation and puncture in mice.
Results
Pre-treatment with anti-TLR2 or anti-TLR4 mAb alone showed significant protection from sepsis-associated death. Protective effects were observed even when the administration of either anti-TLR2 or anti-TLR4 alone was delayed (i.e., 3 h after sepsis induction). Delayed administration of either mAb in combination with antibiotics resulted in additive protection.
Conclusion
Although attempts to translate preclinical findings to clinical sepsis have failed so far, our preclinical experiments strongly suggest that there is a sufficient therapeutic window within which patients with ongoing sepsis could benefit from combined antibiotic plus anti-TLR2 or anti-TLR4 mAb treatment.
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