Regulation of peritoneal and systemic neutrophil-derived tumor necrosis factor-α release in patients with severe peritonitis: Role of tumor necrosis factor-α converting enzyme cleavage

• Published in: Critical care medicine Vol. 33; no. 6; pp. 1359 - 1364
• Main Authors: Kermarrec, Nathalie, Selloum, Saphia, Plantefeve, Gaetan, Chosidow, Denis, Paoletti, Xavier, Lopez, Anne, Mantz, Jean, Desmonts, Jean-Marie, Gougerot-Pocidalo, Marie-Anne, Chollet-Martin, Sylvie
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD by the Society of Critical Care Medicine and Lippincott Williams & Wilkins 01-06-2005; Lippincott
• Subjects: ADAM Proteins; ADAM17 Protein; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Biomarkers; Blood and lymphatic vessels; Cardiology. Vascular system; Case-Control Studies; Cells, Cultured; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Emergency and intensive care: infection, septic shock; Female; Humans; Intensive care medicine; L-Selectin - metabolism; Male; Medical sciences; Metalloendopeptidases - metabolism; Middle Aged; Neutrophils - metabolism; Peritoneum - metabolism; Peritonitis - complications; Peritonitis - enzymology; Peritonitis - immunology; Prospective Studies; Receptors, Tumor Necrosis Factor - metabolism; Sepsis - complications; Sepsis - enzymology; Sepsis - immunology; Severity of Illness Index; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation; Human; Intensive care; tumor necrosis factor-a; Cytokine; tumor necrosis factor-a converting enzyme; Abdominal disease; Tumor necrosis factor β; Neutrophil; polymorphonuclear neutrophil; Tumor necrosis factor α; Peritonitis; Resuscitation; sepsis
• ISSN: 0090-3493; 1530-0293
• DOI: 10.1097/01.CCM.0000166359.47577.57

OBJECTIVE:Polymorphonuclear neutrophil (PMN) influx and peritoneal tumor necrosis factor (TNF)-α production are key host defense mechanisms during peritonitis. The aim of this study was to explore the potential interactions between TNF-α production and TNF-α 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-α, soluble L-selectin, and type I and II TNF-α receptor levels; 2) PMN membrane TNF-α, membrane L-selectin, and TACE expression (flow cytometry); and 3) TNF-α production by cultured PMN. Correlations between these forms of PMN-derived TNF-α and the severity of the peritonitis and patient’s outcome were investigated.
MAIN RESULTS:Elevated soluble TNF-α levels in both plasma and peritoneal fluid from the patients were found, together with decreased expression of membrane TNF-α 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-α in vitro, in optimal conditions of stimulation (lipopolysaccharide + interferon-γ), was impaired as compared with controls’ blood PMN. Regulation of PMN-derived TNF-α 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-α, L-selectin, and TNF receptors.