Fusidin ameliorates experimental autoimmune myocarditis in rats by inhibiting TNF-alpha 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-alpha (TNF-alpha) 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-alpha 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-a compared with vehicle-treated animals. Similarly, TNF-alpha 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-alpha.
Department of Microbiology and Immunology, Faculty of Pharmacy, Belgrade, Serbia. marinama@pharmacy.bg.ac.yu
M
M
Milenkovć
N
N
Arsenović-Ranin
D
D
Vucićević
B
B
Bufan
Z
Z
Stojić-Vukanić
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D005672:Fusidic Acid / Q000627:therapeutic use*; D008198:Lymph Nodes / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D009205:Myocarditis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011500:Protein Synthesis Inhibitors / Q000627:therapeutic use*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D005672:Fusidic Acid