Release of Soluble Receptors for Tumor Necrosis Factor in Clinical Sepsis and Experimental Endotoxemia

To assess the role of tumor necrosis factor (TNF) in the appearance of soluble TNF receptors (sTNFRs), 20 consecutive patients with a clinical diagnosis of sepsis were studied as were 7 chimpanzees after administration of endotoxin (4 ng/kg) with or without pentoxifylline. The patients had markedly elevated serum levels of sTNFR-p55 and sTNFR-p75 compared with healthy controls (P < .0001 for both receptors). The levels of both soluble receptors correlated with simultaneously measured immunoreactive TNF concentrations (p55: r = .63, P < .01; p75: r = .69, P < .001). In the chimpanzees, endotoxin induced subsequent rises in the serum concentrations ofTNF and sTNFRs. Although pentoxifylline reduced the TNF response to intravenous endotoxin to 20% (P < .05), the appearance of sTNFRs was only moderately inhibited (sTNFR-p55 to 79% on average, P < .05; sTNFR-p75 to 77%, P = .12). These results indicate that TNF either does not play an important role in the appearance of sTNFRs in systemic infection or that a small amount ofTNF remaining in the circulation after some bacterial challenges is sufficient to preserve the secretion of its soluble receptors.