Depression of hepatic mixed-function oxidase activity by B. pertussis in splenectomized and athymic nude mice

Abstract

Administration of Bordetella pertussis (B. pertussis), Corynebacterium parvum (C. parvum), and several other immunoactive substances is known to cause a marked decrease in the activity of the hepatic microsomal mixed-function oxidase system. The effect of C parvum has been reported to involve the reticuloendothelial system. In the present study, the effect of B. pertussis administration to decrease hepatic microsomal drug metabolism was studied in unoperated, sham-operated, and splenectomized mice as well as in athymic nude (nu/nu) mice and their phenotypically heterozygous (+/nu) littermates. Administration of B. pertussis to the splenectomized, sham-operated, and unoperated mice resulted in a decrease in the activity of the microsomal enzyme system that was approximately the same for each of the three groups of animals. Administration of B. pertussis to nu/nu mice and the +/nu mice also decreased the microsomal enzyme activity measured 24 hr after injection. However, at 7 days after B. pertussis administration, the hepatic drug-metabolizing activity of the nu/nu mice was not significantly different from control values, whereas the activity of the +/nu mice was still significantly depressed. The failure of splenectomy to prevent the decrease in microsomal mixed-function oxidase activity caused by B. pertussis indicated that the effect of this agent differs from that of C. parvum, whose effect was prevented by splenectomy. Indeed, the results obtained with the athymic nude mouse suggests that the depression of hepatic mixed-function oxidase activity by B. pertussis may involve T-cell dependent responses.