A model illustrating opposing roles of STAT1 and STAT3 in Con A–induced hepatitis. Con A activates multiple immune cells, including NK T cells and CD4+ T cells, and induces the release of a variety of cytokines. IFN-γ induces activation of JAK1 and JAK2 and consequent activation of STAT1. IFN-γ/STAT1 play an essential role in CD4+ and NK T cell activation, which, in turn, directly or indirectly induce liver injury. IFN-γ/STAT1 also induce expression of proapoptotic IRF-1 protein, which mediates liver apoptosis and injury. IL-6 and IFN-γ activate JAK1 and JAK2 and consequently induce STAT3 activation, followed by induction of Bcl-XL and other antiapoptotic factors, which protect against hepatic necrosis and apoptosis. IL-6 activation of STAT3 also downregulates IFN-γ and IFN-γ signaling and consequently suppresses IFN-γ/STAT1-induced liver injury. Activated STAT1 and STAT3 inhibit one another, at least in hepatocytes, by the induction of SOCS.