Fusidin ameliorates experimental autoimmune myocarditis in rats by inhibiting TNF-α production

Experimental autoimmune myocarditis (EAM) represents a model for human autoimmune myocarditis, a condition for which no optimal treatment is currently available. It has been reported that tumor necrosis factor-α (TNF-α) plays a crucial role in pathogenesis of EAM. The immunomodulating antibiotic fusidic acid and its sodium salt (sodium fusidate-fusidin) were previously shown to reduce TNF-α production and its end-organ cytotoxicity, thus proving beneficial in several animal models of organ-specific autoimmune diseases. To investigate the effects of fusidin on EAM the drug was given at dose 80 mg/kg i.m. to EAM rats. Fusidin was administered as an early, from day 0 to 10, or late treatment, from day 10 to 21, after induction of disease. Both early and late treatment with fusidin markedly ameliorated the clinical and histological signs of the disease. Fusidin-treated rats had significantly decreased blood levels of TNF-α compared with vehicle-treated anim^als. Similarly, TNF-α production by in vitro sensitized lymph node cells in both fusidin treated groups was significantly lower than that in EAM rats. The present findings suggest that fusidin ameliorated EAM, at least partly, through an inhibitory action on the secretion of TNF-α.