FK506 INHIBITS RENAL GLOMERULAR THROMBOSIS INDUCED IN RATS BY NEPHROTOXIC SERUM AND LIPOPOLYSACCHARIDE

We investigated the effect of the potent immunosuppressive agent, FK50 6, on experimental glomerular thrombosis in rats by combined injection s of nephrotoxic;serum (NTS) and lipopolysaccharide (LPS). Either FK50 6 or placebo was administered intramuscularly three hours prior to inj ection of NTS that was followed one hour later by LPS. Rats were kille d five hours after the LPS injection. Compared with placebo, FK506 pre treatment significantly reduced thrombosis formation, in a dose-depend ent manner. FK506 also reduced proteinuria and the rise of serum creat inine level. Early infiltration of polymorphonuclear leukocytes into t he glomeruli after LPS injection was significantly suppressed in the F K506 group compared with the placebo group. We also measured serum tum or necrosis factor (TNF) activity by using an L929 fibroblast cytotoxi city assay. Peak serum TNF activity was observed one hour after LPS in jection, and FK506 significantly suppressed the elevation. Thrombosis was also developed in athymic nude rats, suggesting thrombosis formati on is T cell independent. These data suggest that the FK506 has inhibi tory effects on non-lymphocytes and possesses an anti-inflammatory eff ect in vivo.