Type IV Phosphodiesterase Inhibitor Is Effective in Prevention and Treatment of Experimental Crescentic Glomerulonephritis

Abstract

Background: Tumour necrosis factor alpha (TNF-α) has an important role in acute glomerular inflammation. Rolipram, a type IV phosphodiesterase inhibitor, has multiple anti-inflammatory effects including inhibition of TNF-α synthesis. Methods: We investigated the effects of rolipram in prevention and delayed treatment of crescentic glomerulonephritis in Wistar Kyoto rats. Glomerulonephritis was induced by injection of nephrotoxic serum. Results: In the preventive study, rolipram (6.25 mg/kg i.p. twice daily) was started 2.5 h before injection of nephrotoxic serum. Rolipram reduced the expression of TNF-α in glomeruli and renal tubules and abrogated glomerular injury on day 4 (99.7% reduction in albuminuria and 96.4% reduction in fibrin deposition). In the delayed-treatment experiment, rolipram was started 4 days after injection of nephrotoxic serum. Rolipram reduced renal excretion of TNF-α by 63% on day 7. TNF-α was not detected in the sera of treated or control rats. Delayed treatment was effective in crescentic 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 experimental crescentic glomerulonephritis. This was associated with a reduction of renal production of TNF-α.