Circulating TNF-α and its soluble receptors during experimental acute pancreatitis

Abstract

Clinical and experimental studies have shown increased concentrations of TNF-α and its soluble receptors in serum of patients with acute pancreatitis. In this work, we have investigated the time-course of TNF-α and its soluble receptors during taurocholate-induced acute pancreatitis. In addition, since TNF-α itself could mediate the shedding of its receptors, we have assessed the effect of inhibiting TNF-α production on the release of soluble TNF-α receptors in experimental acute pancreatitis. Our results indicate that soluble receptors are released in the early stages of the disease and this increase is concomitant with the release of TNF-α, which is mainly bound to specific proteins. The increased concentrations of its receptors strongly suggest that they could be these binding proteins. Inhibition of TNF-α generation with pentoxifylline abrogated the shedding of sTNF-αR1, but had no effect on sTNF-αR2. This finding suggests that the shedding of sTNF-αR1 is induced by TNF-α itself, but in the case of sTNF-αR2, the shedding appears to be induced by another mechanism. © 2003 Elsevier Ltd. All rights reserved.