Effect Of Cytokines On Cyp450 System

Razzak et al. (33) examined the role of five cytokines (IL-1P, IL-4, IL-6, TNF-a, and IFN-g) on the expression of CYP1A2, CYP2C, CYP2E1, CYP3A, and epoxide hydrolase in primary human hepatocyte cultures. The results of the study indicated that among these cytokines, IL-1P, IL-6, and TNF-a were the most potent inhibitors of P450 enzymes. After three days of treatment, both mRNA levels and enzyme activities were inhibited by at least 40%. IFN-g suppressed CYP1A2 and CYP2E1 mRNA levels but had no effect on CYP3A and epoxide hydrolase mRNAs. On the other hand, IL-4 increased the CYP2E1 activity up to fivefold, suggesting that different regulatory mechanisms may be involved. This change in drug-metabolizing capacity may be due to a downregulation of P450 gene transcription and RNA modulation.

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