The role of cytokines in the regulation of drug disposition: extended functional pleiotropism?

INTRODUCTION: Drug disposition, metabolism and drug-drug interactions are important considerations for most drugs. Cytokines are integral to the successful resolution of many diseases. Data are emerging on a role for cytokines in regulation of the expression and activity of drug transporters and drug metabolising enzymes. Investigation of the interaction between pharmacological and immunological responses is key to understanding the complex relationships involved in patient response to therapy. AREAS COVERED: Evidence detailing the ability of cytokines to regulate drug disposition and metabolism is reviewed in the context of different cell and tissue types. The literature search undertaken provides an overview of the current understanding of the interrelationship between pharmacological and immunological factors which may influence successful drug therapy. EXPERT OPINION: Dysregulation of cytokines and cytokine networks is a hallmark of a number of diseases such as HIV and cancer. The mechanisms by which the immune system can influence drug disposition are relatively understudied but recent work has highlighted the necessity for examining its impact on pharmacokinetics and pharmacodynamics. A more comprehensive approach in clinical studies will allow better determination of the impact of cytokines on drug disposition. In addition, determining the mechanisms that underpin the differential effects of cytokines across different cell types will clarify the responses reported in these studies.