Gender-related differences in concanavalin A-induced liver injury and cytokine production in mice

Abstract

Background/aim: Concanavalin A (Con A) activates T cells and causes T cell-mediated liver injury in mice. Since autoimmune diseases predominantly occur in women, female is considered to have enhanced immune responses and T cell functions. We investigated the presence of gender-related differences on Con A-induced liver injury and cytokine production in mice. Methods: Male and female BALB/c mice were given Con A (15 mg/kg) intravenously at 7 weeks of age. Plasma alanine aminotransferase (ALT), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin (IL)-4 and IL-10 levels were determined 0, 2, 4, 6, 8 and 24 h after Con A administration. To investigate the effects of sex hormones on liver injury and cytokine production, female and male mice were castrated at 3 weeks of age and were administered Con A 4 weeks after the operation. Results: Plasma ALT level of females was significantly higher at 8 and 24 h after Con A administration than those of males. Plasma levels of TNF-α and IFN-γ at 2, 4, 6 and 8 h, IL-4 at 2 h, but not IL-10, after Con A administration were significantly elevated in females than those of males. Furthermore, the elevated plasma ALT, TNF-α and IFN-γ levels decreased significantly by an ovariectomy. In contrast, those markers were exacerbated by an orchiectomy compared with sham operation. Conclusion: These findings indicate that Con A induces more severe liver injury in female mice than in male mice, and suggest that the effect of sex hormones on cytokine production may play a role in gender-related difference on Con A-induced liver injury.