Opposite effects of high and low doses of interleukin-2 on T cell-mediated hepatitis in mice (interleukin-2 on hepatitis).
OBJECTIVE
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-γ), and tumor necrosis factor alpha (TNF-α), 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.


METHODS
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 × 10(3) U/mouse) and four injections of low dose of rhIL-2 (IL-2(4lo), 5 × 10(3) U/mouse).


RESULTS
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-α while IL-2(4lo) pretreatment did not. Serum IL-4 and TNF-α 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.


CONCLUSIONS
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.
Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027 China.
Xiaoang
X
Zhang
Hua-Xing
HX
Wei
Sun
S
Rui
Haiming
H
Wei
Zhigang
Z
Tian