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

Nephron. 2000 Jan;84(1):58-66. doi: 10.1159/000045539.


Background: Tumour necrosis factor alpha (TNF-alpha) has an important role in acute glomerular inflammation. Rolipram, a type IV phosphodiesterase inhibitor, has multiple anti-inflammatory effects including inhibition of TNF-alpha 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-alpha 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-alpha by 63% on day 7. TNF-alpha 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-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / administration & dosage
  • Basement Membrane / immunology
  • Disease Models, Animal
  • Glomerulonephritis / drug therapy*
  • Glomerulonephritis / pathology
  • Glomerulonephritis / prevention & control*
  • Kidney / metabolism
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Leukocytes / pathology
  • Male
  • Phosphodiesterase Inhibitors / classification
  • Phosphodiesterase Inhibitors / therapeutic use*
  • Rats
  • Rats, Inbred WKY
  • Rolipram / therapeutic use*
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Antibodies
  • Phosphodiesterase Inhibitors
  • Tumor Necrosis Factor-alpha
  • Rolipram