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 th e pathogenesis of glomerular disease. Intrinsic glomerular cells as we ll as extraglomerular cells have been found as a source of TNF-alpha. Rat glomerular mesangial cells produce TNF-alpha after stimulation wit h bacterial lipopolysaccharide (0.1, 1.0 and 10 mu g/ml) over differen t times (4, 8, 16 and 24 h). We show that lipopolysaccharide-induced p roduction of TNF-alpha in rat mesangial cell cultures is inhibited by pentoxifylline (50 mg/ml), cyclosporine A (0.1 mu g/ml) and taurolidin e (100 mg/ml). Inhibition of this production seems to be a promising t reatment option for renal disease. Already pentoxifylline and cyclospo rine A have been shown to improve different glomerular pathologies. Th eir in vitro effect on TNF-alpha production shown here might influence this.