Activated polymorphonuclear neutrophils (PMN) and neutrophil activating mediators such as tumor necrosis factor-alpha (TNF-alpha) are thought to be involved in the pathophysiology of sepsis and multiple organ failure syndrome (MOFS). In critically ill patients at high risk for the development of septic syndrome (n = 17) peripheral blood PMN were assayed for O2- and H2O2 production after stimulation with phorbol myristate acetate (PMA, 40 nM). Serum TNF-alpha levels were determined by ELISA. At the time of admission to the intensive care unit we found significant higher levels of TNF-alpha (P = 0.0001) in the serum of patients finally developing sepsis correlating to higher respiratory burst capability in comparison to nonseptic patients. Additionally we were able to demonstrate a significant (P = 0.0016) lower dismutation rate of O2- to H2O2 in deceased patients in comparison to survivors. These results give further evidence that elevated levels of circulating TNF-alpha and activated PMN play a significant role in the pathogenesis of septic syndrome in critically ill patients.
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