Mechanisms of immune responses by toll-like receptor against Infection and organ failure

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Although surgical insults may induce postoperative immunosuppression, its mechanism remains unknown. The aim of this study was to examine TLR2 and TLR4 expression on monocytes and their responses to each agonist after surgical insults. The subjects were patients who received gastrointestinal surgery. Peripheral blood mononuclear cells (PBMC) at the indicated times were extracted from the patients and their TLR2, TLR4 and inducible nitric oxide synthase (iNOS) expressions were analyzed. TLR2 and TLR4 were rapidly decreased and showed lowest values on the 1st and 3rd postoperative days, respectively. Next, we measured Macrophage-activating lipopeptide-2 (MALP-2)- or lipopolysaccharide (LPS)- induced TNF- α and IL-6 production. MALP-2-stimulated TNF- α and IL-6 production was significantly decreased after surgery and increased to a maximum value on the 1st postoperative day, then gradually decreased. LPS-stimulated TNF- α production was significantly suppressed after surgery then showed a gradual increase to maximum values on the 3rd postoperative day. iNOS in PBMC was significantly induced after surgery. In conclusion, expression of TLR2 and TLR4 was down-regulated by surgery, and agonist-induced cytokine production was transiently suppressed and soon increased through activation of PBMC. The present study may offer new insights for postoperative modulation of innate immunity under surgical stress.