Pentoxifylline, cyclosporine A and taurolidine inhibit endotoxin-stimulated tumor necrosis factor-alpha production in rat mesangial cell cultures.

Tumor necrosis factor-alpha (TNF-alpha) is an important mediator in the pathogenesis of glomerular disease. Intrinsic glomerular cells as well as extraglomerular cells have been found as a source of TNF-alpha. Rat glomerular mesangial cells produce TNF-alpha after stimulation with bacterial lipopolysaccharide (0.1, 1.0 and 10 microg/ml) over different times (4, 8, 16 and 24 h). We show that lipopolysaccharide-induced production of TNF-alpha in rat mesangial cell cultures is inhibited by pentoxifylline (50 mg/ml), cyclosporine A (0.1 microg/ml) and taurolidine (100 mg/ml). Inhibition of this production seems to be a promising treatment option for renal disease. Already pentoxifylline and cyclosporine A have been shown to improve different glomerular pathologies. Their in vitro effect on TNF-alpha production shown here might influence this.