Type IV phosphodiesterase inhibitor is effective in prevention and treatment of experimental crescentic glomerulonephritis

Background: Tumour necrosis factor alpha (TNF-a) has an important role in a cute glomerular inflammation. Rolipram, a type IV phosphodiesterase inhibit or, has multiple anti-inflammatory effects including inhibition of TNF-alph a synthesis. Methods: We investigated the effects of rolipram in prevention and delayed treatment of crescentic glomerulonephritis in Wistar Kyoto rats. Glomerulon ephritis was induced by injection of nephrotoxic serum. Results: In the preventive study, rolipram (6.25 ml/kg i.p. twice daily) wa s started 2.5 h before injection of nephrotoxic serum. Rolipram reduced the expression of TNF-alpha in glomeruli and renal tubules and abrogated glome rular injury on day 4 (99.7% reduction in albuminuria and 96.4% reduction i n fibrin deposition). In the delayed-treatment experiment, rolipram was sta rted 4 days after injection of nephrotoxic serum. Rolipram reduced renal ex cretion of TNF-alpha by 63% on clay 7. TNF-alpha was not detected in the se ra of treated or control rats. Delayed treatment was effective in crescenti c glomerulonephritis, as shown by reduction in albuminuria by 38.1%, fibrin deposition by 60.8%, and crescent formation by 67% on day 7. Conclusions: Rolipram is effective both in prevention and treatment of expe rimental crescentic glomerulonephritis. This was associated with a reductio n of renal production of TNF-alpha. Copyright (C) 2000 S. Karger AG. Basel.