We highly appreciate the comments by Weng and colleagues. Our laboratory has been focusing on the role of inflammation in liver injury, fibrosis, and regeneration by using a model of myeloid cell–specific signal transducer and activator of transcription 3 (STAT3) knockout (STAT3mye−/−) mice. As it was previously reported, STAT3mye−/− mice are highly susceptible to endotoxin shock with increased production of inflammatory cytokines.1 We demonstrated that STAT3mye−/− mice were resistant to liver damage after carbon tetrachloride (CCl4) injection,2 but more susceptible to concanavalin A–induced and ethanol-induced liver damage, accompanied by more inflammatory cells in the liver.3, 4 We believe, as Weng and colleagues summarized, the balance between pro- and anti-inflammatory cytokines determines the fate of hepatocyte survival or death. These results suggest that the etiology of liver injury determines whether inflammatory cells contribute to attenuating or worsening liver damage.
Weng et al. also raised an important point regarding the effect of inflammation on liver fibrogenesis. Although we have not examined CCl4-induced chronic liver injury and fibrosis in STAT3mye−/− mice, the effects of inflammation on fibrogenesis in these mice may be complex. Inflammation not only contributes to fibrogenesis, but also plays an important role in the resolution of liver fibrosis.5 In our study, STAT3mye−/− mice had high levels of liver inflammation associated with higher levels of tumor necrosis factor-α, interleukin-1 (IL-1), and IL-6, which are known to promote liver fibrosis, but also higher levels of IL-10 and interferon-γ, which are known to inhibit liver fibrosis. The balance between these pro- and antifibrogenic cytokines will likely play an important role in determining the progression of liver fibrogenesis in STAT3mye−/− mice after chronic CCl4 treatment.