Lymphokines and bile secretion in the rat.

Sepsis is occasionally accompanied by jaundice which is marked by an intrahepatic cholestasis and scant hepatocyte necrosis. The pathogenesis is unknown. The bile fistula rat was used in this study to investigate the possibility that intrahepatic cholestasis is one of the many systemic effects of the major endogenous pyrogen, interleukin-1. The effect of acute administration of endotoxin, interleukin-2 and recombinant rat interferon gamma on biliary secretion and biliary transport mechanisms was also studied. Basal bile flow, peak bile flow and peak sodium taurocholate output were measured after 1 h in all cases, except with recombinant rat interferon gamma where the time interval was 3 h. Endotoxin significantly reduced basal and sodium taurocholate-stimulated bile flow, as well as sodium taurocholate secretion. No such effect was noted after acute administration of any of these lymphokines or chronic administration of interleukin-1. The cholestasis induced by endotoxin administration is not mediated by interleukin-1, interleukin-2 or recombinant interferon gamma.