OC-041 Enhanced Monocyte Function and Surface TLR Expression Predict Post-Operative Systemic Inflammatory Response Syndrome in Patients Immediately following Major Hepatic and Pancreatic Resection

Abstract

<h3>Introduction</h3> Patients undergoing major surgery are at risk of systemic inflammatory response syndrome (SIRS) and life-threatening post-operative sepsis. Early identification of high-risk patients would allow for tailored post-operative care. We tested the hypothesis that post-operative SIRS could be predicted by differences in innate immune function in peripheral blood mononuclear cells (PBMC) taken from patients undergoing major abdominal surgery in the perioperative period. <h3>Methods</h3> Serial blood samples were taken from consenting, adult patients undergoing major hepatic or pancreatic surgery pre-operatively and on days one and two postoperatively. Patients with inflammatory co-morbidities, pre-operative sepsis and those taking anti-inflammatory or immunomodulatory medication were excluded. PBMCs were isolated, stimulated for 24 hours with lipopolysaccharide (LPS) or flagellin and cytokine production was quantified by ELISA. PBMC surface expression of CD14, TLR4 and TLR5 was assessed by flow cytometry. SIRS was defined by the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria. <h3>Results</h3> We included 32 patients, nine of whom developed SIRS on day five or later. There were no significant pre-operative differences between the SIRS and the non-SIRS groups in TLR-induced IL-6 and TNFa production nor TLR4 and TLR5 expression. LPS- and flagellin- induced IL-6 concentrations were significantly greater in the SIRS group on day two (1532pg/µl vs 153pg/µl; p &lt; 0.0002). Monocyte expression of both TLR4 and TLR5 was significantly greater in the SIRS group on both day one (p &lt; 0.002) and day two (p &lt; 0.001). There was no significant difference in CRP or other clinical predictors of SIRS between the groups in the early post-operative period. <h3>Conclusion</h3> Patients who develop SIRS show increased cytokine production in response to TLR stimulation in the early post-operative period. This is associated with elevated surface TLR4 and TLR5 expression in monocytes. These data indicate that there are early functional differences in innate immune responses in patients who develop SIRS compared to those who do not, and that these differences are detectable days before the onset of clinical symptoms. Such assays can help to identify at-risk patients in whom intensive therapy can be targeted. <h3>Disclosure of Interest</h3> None Declared