VACCINE-INDUCED ALTERATIONS IN HEPATIC DRUG-METABOLISM

Administration of Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed (DTP) vaccine to mice causes dose- and time-dependent alterations in hepatic drug metabolism as determined by hexobarbital-induced sleep time and several direct measurements of soluble and microsomal enzyme activities. Vaccines containing only tetanus and/or diphtheria toxoids did not alter hepatic drug metabolism, implicating the pertussis component as the cause of the observed changes. Other pyrogenic whole cell vaccines such as typhoid and cholera also had no effect on drug metabolizing capacity. However, polyriboinosinic polyribocytidylic acid (poly I:C), a compound thought to exert its effects through the induction of interferon, induced changes comparable to those seen with DTP vaccine. The similarities in the effects following administration of DTP vaccine and poly I:C suggest that vaccine-induced alterations of drug metabolism may be mediated by immunomodulatory agents such as interferons and interleukins. Studies with purified cytokines are planned to address this question.