Suppression of experimental autoimmune myocarditis by sodium fusidate (fusidin).
Fusidic acid and its sodium salt sodium fusidate (fusidin) are widely used antibiotics that possess immunomodulating properties. It has been shown that fusidin ameliorates the course of several organ-specific immunoinflammatory diseases and thus we investigated the effect of fusidin on myosin-induced experimental autoimmune myocarditis (EAM) in rats, a well-established animal model for human giant cell myocarditis and postmyocarditis dilated cardiomyopathy (DCM). Fusidin at doses of 80 mg kg(-1) was administrated i.m. to male Dark Agouti (DA) rats, either from days 0 to 10 (early treatment group), or from days 10 to 20 (late treatment group) after induction of EAM. Efficacy of fusidin treatment was determined on day 21 of EAM development. It was observed that both early and late treatment with fusidin markedly ameliorated clinical, histological and immunohistochemical signs of the disease. The treated rats had significantly decreased incidence of EAM, heart weight and heart weight/body weight ratio (Hw/Bw) compared with untreated animals. In contrast to the severe myocardial damage and cellular infiltration in the EAM rats, there was only focal infiltration of inflammatory cells in the myocardium of the treated rats. In both treated groups the mean microscopic score was markedly lower compared with vehicle-treated animals. In addition, the number of CD4+, ED1+ and OX6+ cells was significantly lower in myocardium of fusidin-treated rats than that in untreated group. The present findings suggest that fusidin exhibited both early and late therapeutical effect in EAM.
Milenković
M
M
Department of Microbiology and Immunology, University School of Pharmacy, Faculty of Pharmacy, Belgrade (Kumodraz), Serbia and Montenegro. marinama@pharmacy.bg.ac.yu
Vucićević
D
D
Milosavljević
P
P
Ranin
N Arsenović
NA
Vukanić
Z Stojić
ZS
Colić
M
M
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D005672:Fusidic Acid / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D009205:Myocarditis / Q000188:drug therapy* / Q000276:immunology; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D014409:Tumor Necrosis Factor-alpha; D005672:Fusidic Acid; D007371:Interferon-gamma