Objective To investigate the therapeutic efficacy of Janus kinase 1 (JAK1) inhibitor of Itacitinib (ITA) on autoimmune hepatitis (AIH) in mice. Methods A total of 30 male BALB/c mice were randomly divided into three groups with 10 mice in each group: a blank control group, a model group, and an ITA group. AIH models were established by tail vein injection of concanavalin A (Con A) at a dose of 25 mg/kg in the model and ITA groups, while the control group received an equal volume of normal saline. Thirty minutes after modeling, the ITA group was intraperitoneally administered ITA (10 mg/kg), whereas the control and model groups received an equal volume of saline. All mice were euthanized for 8 hours after the Con A injection, and serum and liver tissue samples were collected. Histopathological changes in liver tissues were observed using HE staining, and serum levels of liver function markers, inflammatory cytokines, as well as the infiltration proportions of CD3+ T cells and CD4+ T cells in liver tissue were measured. Results Compared with the blank control group, the model group exhibited significant liver enlargement, congestion, and spotted hemorrhages, disordered hepatic lobule structure and extensive hepatocellular necrosis; serum levels of ALT and AST, as well as TNF-α, IL-6, and IL-2 concentrations were significantly elevated; infiltration proportions of both CD3+ T cells and CD4+ T cells in the liver tissues also increased (P<0.05), indicating statistically significant differences. Compared with the model group, the ITA group showed obvious improvements in liver appearance and pathological structure, with reduced areas of liver damage, decreased serum ALT and AST levels and lower levels of TNF-α and IL-6; infiltration ratios of CD3+ T cells and CD4+ T cells in the liver tissue were also reduced (all P< 0.05), showing statistically significant differences. Conclusions ITA can effectively alleviate liver damage in Con A-induced AIH mice, possibly through inhibition of the JAK1 signaling pathway, thereby reducing T lymphocyte infiltration and the release of inflammatory cytokines(TNF-α, IL-6, and IL-2).
Key words
JAK1 inhibitor /
autoimmune hepatitis /
Itacitinib /
concanavalin a /
inflammatory cytokines
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