To investigate the roles of tumor necrosis factor-alpha (TNF-alpha), endothelin-1 (ET-1) and thrombomodulin (TM) in the plasma of patients with sepsis, plasma levels of endotoxin (Et), TNF-alpha, ET-1 and TM were determined in 30 such patients. Plasma levels of Et, TNF-alpha, ET-1 and TM at the time sepsis was diagnosed were 4.0 +/- 6.7 pg/ml, 98.5 +/- 92.1 pg/ml, 7.0 +/- 4.1 pg/ml and 7.8 +/- 3.3 ng/ml, respectively. There was no significant difference in the plasma Et level between the group of patients that survived (n = 13) or died (n = 17). Plasma levels of TNF-alpha, Et-1 and TM were significantly higher in the group that died than in the surviving group (TNF-alpha, p < 0.0001; ET-1, p = 0.028; TM, p = 0.0004). There were significant correlations between the plasma levels of TNF-alpha and ET-1, of TNF-alpha and TM, and of ET-1 and TM (r = 0.37, p < 0.046; r = 0.61, p = 0.0008; r = 0.63, p = 0.004), respectively. Results suggest that TNF-alpha is involved in the production of ET-1 and TM. Both of those substances appear to be involved in the morbidity of sepsis, and their plasma levels reflect its severity.
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