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 (similar to 60% inhibition) induced by zymosan, with no effect upon interleukin-la levels. This action was not accompanied by changes in neutrophil accumulation, but the amount of elastase released in the lavage fluids was significantly reduced (similar to 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 (similar to 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.