Type IV phosphodiesterase inhibitor is effective in prevention and treatment of experimental crescentic glomerulonephritis.
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.
Tam
F W
FW
Renal Section, Division of Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, UK. f.tam@ic.ac.uk
Smith
J
J
Agarwal
S
S
Karkar
A M
AM
Morel
D
D
Thompson
E M
EM
Pusey
C D
CD
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D001485:Basement Membrane / Q000276:immunology; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D007668:Kidney / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000145:classification / Q000627:therapeutic use*; D051381:Rats; D011921:Rats, Inbred WKY; D020889:Rolipram / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000906:Antibodies; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D020889:Rolipram