Innate immunity and alcoholic liver fibrosis

The hepatic innate immune system consists of predominant innate immunity, which plays an important role in innate defense against infection and tumor transformation. Emerging evidence suggests that innate immunity also contributes to liver injury, repair, and fibrosis. The present review summarizes the recent findings on the role of innate immunity in liver fibrosis. In general, Kupffer cells stimulate liver fibrosis via production of reactive oxygen species and pro-inflammatory cytokines, whereas natural killer (NK) cells inhibit liver fibrosis by directly killing activated hepatic stellate cells and production of gamma-interferon (IFN-gamma). Complement components, interferons, and Toll-like receptors have also been shown to regulate liver fibrosis. Recent evidence also suggests that modulation of innate immunity by alcohol plays an important role in the pathogenesis of alcoholic liver fibrosis. These include alcohol amplification of the profibrotic effects of Kupffer cells and suppression of the antifibrotic effects of NK/IFN-gamma.