Inhibition of concanavalin A-induced acute T cell dependent hepatic damagein mice by hypothyroidism

Aims/Background: Concanavalin A (Con A) activates T lymphocytes and causes acute T-cell-mediated hepatic injury in mice. Decreased thyroid hormonal pr oduction is associated with a variety of immunological manifestations, incl uding inactivation of macrophages with reduced TNF production and reduced s oluble IL-2 receptors in the serum. We have recently shown that hypothyroid ism prevents the development of cirrhosis and also minimizes hepatic damage in rats with fulminant hepatic failure. In the present study we examined t he effects of hypothyroidism on a mouse model of Con A induced T cell-media ted acute hepatitis. Methods: Hypothyroidism was induced both medically (MM I, PTU) and surgically. Eight groups of 10 mice each were studied: euthyroi d controls (2 groups: water, Con A) and hypothyroid (6 groups: MMI, PTU, Su rgical, MMI-Con Al PTU-Con A, Surgical-Con A). Results: Hepatic inflammatio n was significantly decreased in each of the Con A treated hypothyroid grou ps of mice. The serum transaminases, TNF-alpha and IL-6 levels were signifi cantly elevated in the Con A treated group while near normal levels were fo und in the hypothyroid Con A treated groups (mean+/-SE AST: 1499+/-18 vs 78 +/-10 IU/I, p<0.001; TNF: 2500+/-250 vs 135+/-15 pg/ml, p<0.001, IL-6: 12,2 00+/-300 vs 1260+/-140 pg/ml, p<0.001, respectively). Conclusions: Hypothyr oidism, independent of the mode of induction, can effectively inhibit the d evelopment of acute T cell-mediated liver damage in mice. These results sug gest that some decrease in thyroid function might have a role in the preven tion of immune mediated liver diseases.