During inflammation and infection, overexpression of cytokines is associated with changes in cytochrome P450 (CYP) activities. The present study investigated the effect of cytokines on expression of the glutathione S-transferases (GST), phase II enzymes, involved in drug detoxication and in protection against lipid peroxidation. Human hepatocytes in primary culture were exposed to interleukin 6 (IL6), a proinflammatory cytokine and interleukin 4 (IL4) thought to be an anti-inflammatory cytokine and known to induce CYP2E1 specifically. After a three-day treatment, no reproducible effects of IL-6 could be demonstrated on either GSTA1 and/or A2 or M1 mRNA levels (GSTA1 and A2 were not discriminated by the cDNA probe). In contrast, GSTA1 and/or A2 mRNAs and GSTA1 and A2 proteins were reproducedly increased after IL4 treatment. This increase was blocked by alpha-amanitin, suggesting that active transcription is necessary and was associated with increased AP1 binding activities. These results provide evidences that IL4 exerts important effects on detoxifying hepatic drug metabolizing enzymes.