Interleukin 4 inhibits the production of some acute-phase proteins by human hepatocytes in primary culture.
Interleukin 4 (IL4) has been shown to exhibit anti-inflammatory effects by inhibiting the secretion by monocytes of proinflammatory cytokines such as interleukin 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 alpha 1-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.
Loyer
P
P
Institut National de la Santé et de la Recherche Médicale, Unité de Recherches Hépatologues U-49, Hôpital Pontchaillou, Rennes, France.
Ilyin
G
G
Abdel Razzak
Z
Z
Banchereau
J
J
Dezier
J F
JF
Campion
J P
JP
Guguen-Guillouzo
C
C
Guillouzo
A
A
D000209:Acute-Phase Proteins / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism
D000209:Acute-Phase Proteins; D015850:Interleukin-6; D012333:RNA, Messenger; D015847:Interleukin-4