Search

OBJECTIVE:: Polymorphonuclear neutrophil (PMN) influx and peritoneal tumor necrosis factor (TNF)-a production are key host defense mechanisms during peritonitis. The aim of this study was to explore the potential interactions between TNF-a production and TNF-a converting enzyme (TACE) expression by PMN in the blood and peritoneum of patients with severe peritonitis. DESIGN:: A prospective study. SETTING:: A surgical adult intensive care unit in a university hospital. PATIENTS:: A total of 29 consecutive immunocompetent patients with severe sepsis within 48 hrs of onset were enrolled and underwent laparotomy for a diffuse secondary peritonitis. Thirteen volunteers served as controls. MEASUREMENTS:: Blood and peritoneal fluid recovered during laparotomy were analyzed and compared for 1) soluble TNF-a, soluble L-selectin, and type I and II TNF-a receptor levels; 2) PMN membrane TNF-a, membrane L-selectin, and TACE expression (flow cytometry); and 3) TNF-a production by cultured PMN. Correlations between these forms of PMN-derived TNF-a and the severity of the peritonitis and patients outcome were investigated. MAIN RESULTS:: Elevated soluble TNF-a levels in both plasma and peritoneal fluid from the patients were found, together with decreased expression of membrane TNF-a and TACE up-regulation at the PMN surface. Soluble L-selectin and type I and II TNF receptors were highly released, suggesting also the role of TACE. In contrast, the capacity of both blood and peritoneal PMN to synthesize TNF-a in vitro, in optimal conditions of stimulation (lipopolysaccharide + interferon-?), was impaired as compared with controls blood PMN. Regulation of PMN-derived TNF-a was similar in the two compartments, but responses were more pronounced in the peritoneum. TACE up-regulation at the surface of blood-derived PMN correlated with the Sequential Organ Failure Assessment score and vital outcome. CONCLUSION:: These human data demonstrate that mTACE is up-regulated at the PMN surface during severe peritonitis. This finding could be related to a paracrine regulatory loop involving some TACE substrates such as TNF-a, L-selectin, and TNF receptors. [ABSTRACT FROM AUTHOR]