Inflammatory conditions and cytokines and their roles in the regulation of heme and drug metabolism

It has been well known that inflammation leads to the decreased ability of drug metabolism in human and animals.Since many inflammatory and anti-inflammatory cytokines produced under the inflammatory conditions,their possible roles in the regulation of drug metabolizing enzymes,specifically cytochrome P450s(CYPs),have been examined to date.Lipopolysaccharide (LPS) produces many cryokines and decreases drug medabolism.LPS is also a potent inducer of heme oxygenase(HO-1).We found that LPS produced the induction of HO-1 via TNFα rather than IL-1,be employing each cytokine knockout mice.Additionally,arthritis model mice exhibited the increase in HO-1 without any changes in total CYP content.Effects of chemicals on HO-1 and CYPs in cytokine knockout mice will also be discussed.