FK506 inhibits renal glomerular thrombosis induced in rats by nephrotoxic serum and lipopolysaccharide.

Abstract

We investigated the effect of the potent immunosuppressive agent, FK506, on experimental glomerular thrombosis in rats by combined injections of nephrotoxic serum (NTS) and lipopolysaccharide (LPS). Either FK506 or placebo was administered intramuscularly three hours prior to injection of NTS that was followed one hour later by LPS. Rats were killed five hours after the LPS injection. Compared with placebo, FK506 pretreatment significantly reduced thrombosis formation, in a dose-dependent manner. FK506 also reduced proteinuria and the rise of serum creatinine level. Early infiltration of polymorphonuclear leukocytes into the glomeruli after LPS injection was significantly suppressed in the FK506 group compared with the placebo group. We also measured serum tumor necrosis factor (TNF) activity by using an L929 fibroblast cytotoxicity assay. Peak serum TNF activity was observed one hour after LPS injection, and FK506 significantly suppressed the elevation. Thrombosis was also developed in athymic nude rats, suggesting thrombosis formation is T cell independent. These data suggest that the FK506 has inhibitory effects on non-lymphocytes and possesses an anti-inflammatory effect in vivo.