In vivo consequences of liver-specific interleukin-22 expression: implications for human liver disease progression (117.7)

Abstract

Interleukin 22 (IL-22), which acts as either a pro-inflammatory or anti-inflammatory cytokine in various disease models, is markedly upregulated in chronic liver diseases, including viral hepatitis B and C infection. In this report, we demonstrate a strong correlation between IL-22 expression in the liver with active, inflammatory human liver disease. To clarify the role of IL-22 upregulation in the pathogenesis of liver diseases, liver specific IL-22 transgenic (IL-22TG) mice, under the control of albumin promoter, were developed. Despite elevated IL-22 serum levels ranging from 4000 to 7000 pg/ml, IL-22TG mice developed normally without obvious adverse phenotypes or evidence of chronic inflammation. Most interestingly, IL-22 TG mice were completely resistant to Concanavalin A-induced T cell hepatitis with minimal effect on liver inflammation and had accelerated liver regeneration after partial hepatectomy. Although they did not spontaneously develop liver tumors, IL-22 TG mice were more susceptible to diethylnitrosamine-induced liver cancer. Microarray analyses revealed that a variety of anti-oxidant, mitogenic, acute phase genes were upregulated in the livers from IL-22TG mice compared with those from wild-type mice. These findings indicate that localized production of IL-22 in the liver promotes hepatocyte survival and proliferation but primes the liver to be more susceptible to tumor development without significantly affecting liver inflammation.