The Mechanism of How Anti-IL-18 Prevents Concanavalin-A-Induced Hepatic Fibrosis on a Mouse Model

BackgroundThe administration of concanavalin A (ConA) induces severe hepatic fibrosis in mice. Tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) 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 methodsOne hundred eighty BABL-C mice were randomly divided into five groups (Group a, b, c, d, e). The mice were administered saline, immunoglobulin G, ConA, IL-18 + ConA, Anti-IL-18 + ConA, respectively. At 1, 7, 14, 21 wk, the levels of serum alanine aminotransferase, TNF-α, IFN-γ, IL-4, matrix metalloproteinase (MMP)-2-RNA, and tissue inhibitor of metalloproteinase-1-mRNA were measured.ResultsThe levels of serum TNF-α and IFN-γ detected in the IL-18 + ConA group was higher than in the anti-IL-18 + ConA group (P < 0.05). Similarly, the levels of MMP-2-RNA and tissue inhibitor of metalloproteinase-1-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.ConclusionsThe 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.