title: Regulation of drug-metabolizing enzymes and transporters in infection, inflammation, and cancer.
abstract: This article is a report on a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 07 meeting in Washington, DC. The presentations discussed the phenomenology, clinical consequences, and underlying mechanisms of cytochrome P450 and drug transporter regulation by inflammatory and infectious stimuli. Although considerable insights into the links between inflammatory mediators and altered hepatic drug clearance pathways have been gained from previous studies with acute inflammatory stimuli, this symposium highlighted recent advances in understanding how these processes operate in other organs and chronic inflammatory states relevant to human diseases. The development of mouse models of live bacterial infection provides excellent opportunities to explore the impact of infection on drug metabolism beyond the well characterized effects of bacterial endotoxin. Altered levels of cytochromes P450 and especially drug transporters due to inflammation in brain, intestine, and placenta have significant implications for the use of many drugs in diverse clinical settings. The consequences of inflammatory cytokine production by tumors for drug safety and efficacy in cancer patients were outlined. Repression of drug clearance pathways by tumor-derived cytokines may result in extreme toxicity to chemotherapy, compromising treatment of many cancers. It is fitting that, in honoring the career contributions and achievements of Dr. Kenneth W. Renton, this symposium reinforced the clinical relevance of this field.
authors.affiliation: Department of Pharmacology, Emory University, Atlanta, GA 30322, USA. etmorga@emory.edu
authors.forename: Edward T
authors.initials: ET
authors.lastname: Morgan
authors.forename: Kerry B
authors.initials: KB
authors.lastname: Goralski
authors.forename: Micheline
authors.initials: M
authors.lastname: Piquette-Miller
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Renton
authors.forename: Graham R
authors.initials: GR
authors.lastname: Robertson
authors.forename: Madhusudana R
authors.initials: MR
authors.lastname: Chaluvadi
authors.forename: Kellie A
authors.initials: KA
authors.lastname: Charles
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Clarke
authors.forename: Marina
authors.initials: M
authors.lastname: Kacevska
authors.forename: Christopher
authors.initials: C
authors.lastname: Liddle
authors.forename: Terrilyn A
authors.initials: TA
authors.lastname: Richardson
authors.forename: Rohini
authors.initials: R
authors.lastname: Sharma
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sinal
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007239:Infections / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System