DRUG-CYTOKINE INTERACTIONS - MECHANISMS AND CLINICAL IMPLICATIONS

The potential for certain cytokines to alter cytochrome P450-mediated drug metabolism was first described over 20 years ago. Since that time , a number of in vitro studies in a variety of models have confirmed t hose observations and evaluated the possible mechanisms. Although the actual mechanism(s) remains unknown, several potential theories have b een proposed, including the inhibition of mRNA transcription, increase d haem oxygenase activity, increased xanthine oxidase activity and the induction of killer cells cytotoxic to liver cells containing cytochr ome P450. Clinical data regarding drug-cytokine interactions are curre ntly limited to the results of studies with small patient numbers and case reports. In addition, the results of different reports are often conflicting. Some clinical studies have reported associations between exogenous or endogenous cytokines and alterations in concomitantly adm inistered drugs, whereas others have reported a lack of effect, Differ ences in cytokine dosages, route of administration, time course of the rapy, sample collection times and patient variability are all likely t o account for the varied results. In this rapidly expanding field, add itional research will better define the mechanisms of these interactio ns and their clinical implications.