UNCONJUGATED BILIRUBIN INHIBITS IN-VITRO MAJOR HISTOCOMPATIBILITY COMPLEX-UNRESTRICTED CYTOTOXICITY OF HUMAN-LYMPHOCYTES

Septic complications have been major problems in the management of pat ients with obstructive jaundice and neonatal jaundice. This study inve stigates effects of unconjugated bilirubin on lymphocyte-mediated cyto toxicity against human tumor target cells. In vitro exposure of human peripheral blood lymphocytes (PBL) with bilirubin IX alpha in bovine a lbumin solution resulted in a dose-dependent decrease of both natural killer activity and antibody dependent cellular cytotoxicity (ADCC) ac tivity, Inhibition of both activities correlated with the amounts of i ntracellular bilirubin. Expression of cell surface CD16, CD56 antigen, and IL-2 receptor beta chain was unchanged in bilirubin-treated PBL a s compared to bilirubin-untreated PBL. When bilirubin-treated PBL were cultured with interleukin-2 (IL-2), a dose-dependent decrease of lymp hokine-activated killing activity, ADCC activity, and DNA synthesis wa s observed. Expression of CD56 antigen and IL-2 receptor a chain was u nchanged in bilirubin-treated PBL following IL-2 stimulation as compar ed to bilirubin free control, These results suggest that bilirubin inh ibits major histocompatibility complex-unrestricted cytotoxicity in bo th unstimulated and IL-2 stimulated lymphocytes. These observations ma y help explain the increased susceptibility to infection observed in h yperbilirubinemic patients.