The mechanism of how Anti-IL-18 prevents concanavalin-A-induced hepatic fibrosis on a mouse model

Background. The administration of concanavalin A (ConA) induces severe hepatic fibrosis in mice. Tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) were the key cytokines involved in the process. The aim of this research was to explore the effects and the mechanisms of IL-18 and anti-IL-18 on hepatic fibrosis in a ConA induced hepatic fibrosis model in BABL-C mice. Materials and methods. One hundred eighty BABL-C mice were randomly divided into five groups (Group a, b, c, d, e). The mice were administered saline, immu-noglobulin G, ConA, IL-18 + ConA, Anti-IL-18 + ConA, respectively. At 1, 7, 14, 21 wk, the levels of serum alanine aminotransferase, TNF-alpha, IFN-gamma, IL-4, matrix metalloproteinase (MMP)-2-RNA, and tissue inhibitor of metalloproteinase-l-mRNA were measured. Results. The levels of serum TNF-a and IFN-y detected in the IL-18 + ConA group was higher than in the anti-IL-18 + ConA group (P < 0.05). Similarly, the levels of NMP-2-RNA and tissue inhibitor of metalloproteinase-l-mRNA expressed in IL-18 + ConA group was higher than in the anti-IL-18 + ConA group (P < 0.05). A majority of these cytokines was secreted by CD4(+)T cells. Conclusions. The immunological response to hepatic fibrosis by repeated injection of ConA in the mouse model was aggravated by IL-18 and blocked by anti-IL-18. (c) 2007 Elsevier Inc. All rights reserved.