EFFECTS OF INTRAVENOUS IMMUNOGLOBULINS ON T-CELL MEDIATED, CONCANAVALIN A-INDUCED HEPATITIS IN MICE

Concanavalin A (ConA) activates T lymphocytes and causes T-cell mediat ed hepatic injury in mice. The intravenous administration of human imm unoglobulins has beneficial effects in T-cell mediated diseases such a s experimental autoimmune encephalomyelitis and adjuvant arthritis. In the present study, we examined the effects of intravenous immunoglobu lins in a mouse model of T-cell mediated, acute liver injury induced b y concanavalin A. Balb/c mice were inoculated with 12 mg/kg concanaval in A with or without intravenous immunoglobulins at doses of 0.4, 0.6, 0.8 g/kg body wt. The serum levels of liver enzymes, tumor necrosis f actor-alpha, interferon-gamma and interleukin-6 were assayed 2, 6 and 24 h after concanavalin A administration. Intravenous immunoglobulins did not prevent concanavalin A-induced hepatitis, as manifested by ele vation of serum aminotransferases and histopathological evaluation. Th e serum levels of tumor necrosis factor-alpha in mice pretreated with immunoglobulins, measured 2 h after ConA treatment were reduced, while interferon-gamma levels measured 6 h after ConA inoculation were 5-fo ld higher than control levels. There was no effect of intravenous immu noglobulins on the release of interleukin 6. In conclusion, these resu lts indicate that intravenous immunoglobulin is not effective in preve nting T-cell mediated concanavalin A-induced hepatitis. The increased secretion of interferon-gamma and the incomplete suppression of tumor necrosis factor-alpha release may explain the lack of efficacy of intr avenous immunoglobulin in this experimental model.