Effects of sodium fusidate in animal models of insulin-dependent diabetes mellitus and septic shock.

摘要: We have evaluated the effects of novel immunosuppressant sodium fusidate (fusidin) in non-obese diabetic (NOD) mouse and D-galactosamine (D-Gal)-presensitized BALB/c mice challenged with bacterial superantigen, Staphylococcus aureus enterotoxin B (SEB) or endotoxin, Escherichia coli lipopolysaccharide (LPS). The NOD model has clinical histoimmunological features similar to those human insulin-dependent diabetes mellitus (IDDM). SEB- LPS-treated models exhibit pathogenic similarities septic shock conditions. In mouse, fusidin suppressed spontaneous development insulitis (mean inhibition 73%) hyperglycaemia (IDDM incidence 25% versus 0%) when administered at 40 mg/kg five times weekly for 8 consecutive weeks from fourth week age; concurrently treated animals exhibited reduced percentages splenic T lymphocytes. This anti-diabetogenic effect was confirmed accelerated induced cyclophosphamide (CY) 55% 21-6% using dosages 80 weekly); protection IDDM achieved even drug (80 mg/kg/day) first 7 days after CY challenge. contrast, did not reverse CY-treated within 3 development. two shock, prophylactic treatment fusidin, given three 2 prior D-Gal/SEB D-Gal/LPS challenge, drastically lethality compared D-Gal/buffer-treated mice. may depend on inhibitory action secretion cytokines such as interferon-gamma tumour necrosis factor-alpha, serum levels which were greatly diminished fusidin-treated 50-90%). These results demonstrate that a role cell-mediated autoimmune diseases cytokine-mediated infectious humans.