Therapeutic Effects of Treatment with Anti-TLR2 and Anti-TLR4 Monoclonal
Antibodies in Polymicrobial Sepsis
#MMPMID26147469
Lima CX
; Souza DG
; Amaral FA
; Fagundes CT
; Rodrigues IP
; Alves-Filho JC
; Kosco-Vilbois M
; Ferlin W
; Shang L
; Elson G
; Teixeira MM
PLoS One
2015[]; 10
(7
): e0132336
PMID26147469
show ga
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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