A beneficial role of bile pigments as an endogenous tissue protector: anti-complement effects of biliverdin and conjugated bilirubin.

Bile pigments possess an anti-complement property and could be involved in tissue protection. In this study, we examined the physiological actions of bile pigments, which had been generally regarded as waste catabolites. Biliverdin inhibited complement cascade reactions in vitro, especially at the C1 step in the classical pathway at low micromolar concentrations. Further, Forssman anaphylaxis in guinea pigs, being closely associated with complement reactions, was inhibited by oral or intravenous administration of biliverdin. Conjugated bilirubin also showed an inhibitory effect on complement-dependent reactions in vitro. From these observations, we propose a hypothesis that the pigments serve as endogenous tissue protectors by multiple lines of mechanisms including antioxidant and anti-complement actions.