Effect of rolipram in a murine model of acute inflammation: comparison with the corticoid dexamethasone

Abstract

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-α (TNF-α) in the lavage fluids (∼ 60% inhibition) induced by zymosan, with no effect upon interleukin-1α levels. This action was not accompanied by changes in neutrophil accumulation, but the amount of elastase released in the lavage fluids was significantly reduced (∼ 50%). Dexamethasone (1.5 mg kg −1, i.v.), used for comparative purposes, significantly reduced the release of TNF-α (> 50%), interleukin-1α (> 70%) and cellular infiltration (∼ 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-α production at a local site of inflammation, such as the subcutaneous air-pouch, and prevented the full activation of migrated cells.