Interleukin 2 induction of cytochrome P450-linked monooxygenase systems of rat liver microsomes

The effects of interleukin 2 (IL-2), a pivotal cytokine for generating an effective immune response, on rat liver microsomal cytochrome P450-linked monooxygenase systems were investigated by measuring the contents of cytochromes b5 and P450, and the activities of various xenobiotic-metabolizing enzymes [debrisoquine and bufuralol monooxygenases (CYP2D), 7-ethoxycoumarin O-deethylase, benzphetamine N-demethylase, aniline hydroxylase and p-nitroanisole N-demethylase]. The enzymatic activities except for p-nitroanisole N-demethylase and aniline hydroxylase were increased approximately to 1.3-fold of those of untreated liver microsomes following intraperitoneal injection of IL-2 (15 U/rat). However, the amount of immunoreactive b5 protein, and the activities of aniline hydroxylase and p-nitroanisole N-demethylase were not changed by injection of IL-2. To elucidate further the mechanism of the induction of CYP2D by IL-2, quantitative analyses of immunoreactive CYP2D protein and its mRNA were conducted by western blot and slot blot hybridization analyses. The results indicated that IL-2 induced an increase in the amounts of immunoreactive CYP2D protein and its mRNA. These enzymatic activities were thus up-regulated at the mRNA level.