Role of inflammatory cytokines in the regulation of hepatic cytochrome P450 expressions after cecal ligation and puncture-induced sepsis

Abstract

We examined how each cytokine is involved in P450 down-regulation in clinical sepsis model by cecal ligation and puncture (CLP). CLP significantly down-regulated CYP1A2, CYP2C29, and CYP3A11 in IL-1α/β KO and TNFα KO mice as well as that in wild-type mice. In contrast, CLP showed no significant effect on CYP1A2 and CYP3A11 in IL-6 KO mice. CYP2C29 was also decreased by CLP in IL-6 KO mice, although the reduced level was less than WT mice. The respective P450 activities were reflected in P450 gene expressions. These results suggest that IL-6 released by CLP down-regulates P450 gene expression.