In vivo anti-complement effect of bilirubin-IXalpha

The effect of the IXalpha isomer of unconjugated bilirubin (UB) on complement-mediated intravascular hemolysis was evaluated in rats carrying naturally occurring heteroantibodies against sheep erythrocytes. Several doses of UB were administered i.v. to these animals in order to induce different levels of hyperbilirubinemia. Intravascular hemolysis was promoted by transfusion with a sheep red cell suspension. Hemoglobin in urine was assessed as a marker of intravascular hemolysis. The urinary excretion of hemoglobin was attenuated by UB in a dose-dependent manner. To establish whether complement was involved in the hemolytic reaction, we evaluated the hemolytic activity of complement in these same animals, before and after sheep erythrocyte transfusion. The significant consumption of complement, which was partially prevented by UB, corroborated its participation in the intravascular hemolytic reaction in the current experimental conditions. The data suggest an inhibitory action of UB on complement-mediated hemolysis in vivo.