Opposite effects of high and low doses of interleukin-2 on T cell-mediated hepatitis in mice (interleukin-2 on hepatitis)

Concanavalin A (Con A)-induced hepatitis is an extensively used animal model of T cell-mediated acute hepatitis. A variety of cytokines, including interleukin 4 (IL-4), interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha), have been shown to play important roles in Con A-induced liver injury. However, the role of IL-2, a critical cytokine in the development and function of T cells and a clinical therapeutics for virus infection and tumor, has not been carefully examined in this model. In this study, we investigated the function of IL-2 in Con A-induced hepatitis by using various strategies of rhIL-2 pretreatment. We treated mice with two rhIL-2 administration strategies: a single injection of high dose of rhIL-2 (IL-2(hi), 50 x 10(3) U/mouse) and four injections of low dose of rhIL-2 (IL-2(4lo), 5 x 10(3) U/mouse). IL-2(hi) pretreatment ameliorated Con A-induced liver injury, while IL-2(4lo) aggravated Con A-induced liver injury. IL-2(hi) pretreatment reduced Con A-induced elevation of serum TNF-alpha while IL-2(4lo) pretreatment did not. Serum IL-4 and TNF-alpha were high 6 h after Con A injection in IL-2(4lo) mice, while it was undetectable in IL-2(hi) and non-pretreated mice. IL-2(hi) pretreatment reduced Con A-induced accumulation of T cells in liver while IL-2(4lo) pretreatment increased accumulation of NK cells. Various strategies of rhIL-2 administration play different roles in Con A-induced hepatitis, suggesting the importance of IL-2 administrative regime in clinical liver diseases.