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Objective: Polymorphonuclear neutrophil (PMN) influx and peritoneal tumor necrosis factor (TNF)-[alpha] production are key host defense mechanisms during peritonitis. The aim of this study was to explore the potential interactions between TNF-[alpha] production and TNF-[alpha] 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-[alpha], soluble L-selectin, and type I and II TNF-[alpha] receptor levels; 2) PMN membrane TNF-[alpha], membrane L-selectin, and TACE expression (flow cytometry); and 3) TNF-[alpha] production by cultured PMN. Correlations between these forms of PMN-derived TNF-[alpha] and the severity of the peritonitis and patient's outcome were investigated.

Main Results: Elevated soluble TNF-[alpha] levels in both plasma and peritoneal fluid from the patients were found, together with decreased expression of membrane TNF-[alpha] 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-[alpha] in vitro, in optimal conditions of stimulation (lipopolysaccharide interferon-[gamma]), was impaired as compared with controls' blood PMN. Regulation of PMN-derived TNF-[alpha] 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-[alpha], L-selectin, and TNF receptors.

(C) 2005 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins