PROTECTION FROM CONCANAVALIN-A (CON-A) INDUCED T-CELL-DEPENDENT HEPATIC-LESIONS AND MODULATION OF CYTOKINE RELEASE IN MICE BY SODIUM FUSIDATE

The immunomodulatory effects of the antibiotic sodium fusidate (SF) we re tested in a model of T cell-dependent hepatic injury that can be in duced in normal mice by a single i.v. injection of Con A. Signs of hep atitis with elevated transaminase activities in plasma, severe infiltr ation of the liver by neutrophil granulocytes, lymphocytes and monocyt es, and necrotic areas were observed in control mice treated intraperi toneally with PBS 24h and 1h before Con A challenge. T cell-and macrop hage-derived cytokines (IL-2, interferon-gamma (IFN-gamma), tumour nec rosis factor-alpha (TNF-alpha), IL-1 beta, IL-6) were released with di fferent kinetics in the circulation of these mice. SF, 20, 40 or 80 mg /kg, administered 24h and 1h before Con A challenge, protected the mic e against the hepatitic effects of Con A. The protective effects of SF were dose-dependent and accompanied by profound modifications of bloo d levels of cytokines induced by Con A, so that, relative to control m ice, SF (80 mg/kg)-treated animals showed markedly diminished plasma l evels of IL-2, IFN-gamma and TNF-alpha, along with augmented levels of IL-6. These results suggest that SF might be useful in the treatment of immunoinflammatory liver diseases in humans.