[Mechanisms of cytokine-induced cholestasis]

Cholestasis is a clinical, biological and histological syndrome that is secondary to the decrease in or disruption of biliary secretion. Clinical or biological cholestasis is common in the course of either infections (parainfectious cholestasis), various cancers (paraneoplastic cholestasis), granulomatosis or in the syndrome accompanying macrophage activation. Cytokine (IL-1, IL-6 and tumor necrosis factor-alpha [TNF-alpha]) synthesis by Kupffer's cells (intrahepatic macrophages) in response to the release of endotoxins occurs in the course of the various clinical syndromes, particularly in the course of sepsis.

Recently, it has been demonstrated that proinflammatory cytokines and endotoxins lead to cholestasis through modulation of the activity of bile acid transporters and other organic anions.

Cholestasis observed in various clinical syndromes in response to either proinflammatory cytokines or endotoxins might be related to a decrease in the flow which is secondary to a decrease in the activity of organic anion transporters.