Interleukin 4 inhibits the production of some acute‐phase proteins by human hepatocytes in primary culture

Abstract
Interleukin 4 (IL4) has been shown to exhibit anti‐inflammatory effects by inhibiting the secretion by monocytes of proinflammatory cytokines such as interieukin 1 (IL1), interleukin 6 (IL6), and tumor necrosis factor (TNF) and by inducing the secretion of the IL1 receptor antagonist. We investigated the role of this cytokine on the production of acute‐phase proteins in primary human hepatocyte cultures. Cells were exposed to either IL4 and/or IL6, the most potent mediator of hepatic acute phase proteins. IL4 led to decreased production of haptoglobin, C‐reactive protein and albumin while α1‐antitrypsin and fibrinogen remained unaffected. These inhibitory effects of IL4 were also observed at the mRNA level. In addition, IL4 inhibited the IL6‐induced production of haptoglobin although it had no effect on the induced C‐reactive protein and fibrinogen. Our results demonstrate that IL4 can affect the production of a subset of acute‐phase proteins by human hepatocytes and can antagonize some of the effects of IL6. These observations reinforce the notion that IL4 can be considered as an anti‐inflammatory cytokine.