Effect of rolipram in a murine model of acute inflammation: comparison with the corticoid dexamethasone.
Treatment of mice with rolipram, a phosphodiesterase type 4 inhibitor, selectively modified the acute inflammatory reaction elicited by zymosan administration in 6-day-old mouse air-pouches. Rolipram (1-10 mg kg-1, i.p.) prevented the rise of endogenous tumor necrosis factor-alpha (TNF-alpha) in the lavage fluids (approximately 60% inhibition) induced by zymosan, with no effect upon interleukin-1 alpha levels. This action was not accompanied by changes in neutrophil accumulation, but the amount of elastase released in the lavage fluids was significantly reduced (approximately 50%). Dexamethasone (1.5 mg kg-1, i.v.), used for comparative purposes, significantly reduced the release of TNF-alpha (> 50%), interleukin-1 alpha (> 70%) and cellular infiltration (approximately 50%), but had only a marginal effect on the release of elastase activity. In conclusion, in this murine model of acute inflammation induced by zymosan, rolipram inhibited the endogenous TNF-alpha production at a local site of inflammation, such as the subcutaneous air-pouch, and prevented the full activation of migrated cells.
Klemm
P
P
Department of Biochemical Pharmacology, William Harvey Research Institute, Medical College of St. Bartholomew's Hospital, London, UK.
Harris
H J
HJ
Perretti
M
M
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D007375:Interleukin-1 / Q000096:biosynthesis; D019272:Leukocyte Elastase; D007962:Leukocytes / Q000473:pathology; D008297:Male; D051379:Mice; D010196:Pancreatic Elastase / Q000187:drug effects / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D020889:Rolipram; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015054:Zymosan
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D015054:Zymosan; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D020889:Rolipram