Role of exogenous interleukin 4 in the dynamics of acute liver injury
Abstract Background Mortality in acute liver failure is very high, and the only reliable treatment is transplantation. Interleukin 4 (IL4) has pleiotropic effects on a network of cells directing repair, regeneration, and fibrosis. Pretreatment with subcutaneous IL4 complexed with anti-IL4 antibody (...
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Veröffentlicht in: | The Lancet (British edition) 2017-02, Vol.389, p.S64-S64 |
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Zusammenfassung: | Abstract Background Mortality in acute liver failure is very high, and the only reliable treatment is transplantation. Interleukin 4 (IL4) has pleiotropic effects on a network of cells directing repair, regeneration, and fibrosis. Pretreatment with subcutaneous IL4 complexed with anti-IL4 antibody (IL4c) promotes repair of carbon tetrachloride-mediated murine liver injury by stimulating hepatocyte proliferation. We hypothesised that IL4c could be administered therapeutically and act by a variety of mechanisms beyond engagement of hepatocytes. Methods C57Bl/6 mice were given carbon tetrachloride intraperitoneally to induce acute liver injury. Preinjury and postinjury dosing regimens of IL4c were compared. The role of IL4 receptor α-chain (IL4Rα) signalling in bone-marrow-derived cells was investigated using tissue-protected chimeras generated with wild type or IL4Rα−/– donor bone marrow. Liver was analysed by immunohistochemistry and fluorescence-activated cell sorting (FACS). Findings When compared with vehicle, administration of IL4c after injury produced a significant reduction in mean alanine aminotransferase (242 U/L [61·9] vs 131 [30·8], p |
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ISSN: | 0140-6736 1474-547X |
DOI: | 10.1016/S0140-6736(17)30460-9 |