Inhibitory effects of bilirubin on cellular immune responses in man

A significant depression in cell-mediated immunity as measured by lymphoproliferative responses to phytohemagglutinin and responsiveness to mixed lymphocyte culture was observed when adult lymphocytes or cord blood lymphocytes were incubated with increasing concentrations of bilirubin. The inhibitory effect of bilirubin could only be demonstrated with suboptimal concentrations of PHA (0.01 and 0.005%) and was more marked in premature infants than in term neonates or adults. This effect was partially reversible after short preincubation with bilirubin, but was more protracted with preincubations of 24 hours or more. Inhibition of MLC responsiveness of 80.1 plus or minus 5.1% was also demonstrated at a bilirubin concentration of 20 mg/dl. Specific cytotoxicity to rubella virus-infected cells, measured by a 51Cr-release microassay, was not found to be depressed. Bilirubin thus appears to have an inhibitory effect on immune responsiveness which is greater on the afferent limb than on the effrent limb of immunity.