Effects of interleukin-10 and modulators of cyclic AMP formation on endotoxin-induced inflammation in rat lung

The aim of this study was to investigate the effects of IL-10, a cell perme able analogue of cyclic AMP, dibutyryl-cAMP (db-cAMP), modulators of intrac ellular cyclic AMP such as phosphodiesterase (PDE) inhibitors and a beta(2) -adrenoceptor agonist, salmeterol, on pulmonary inflammation following acut e lung injury induced by endotoxin exposure in rats. Pulmonary inflammation was induced in adult Wistar rats by a 60-min exposure to endotoxin (lipopo lysaccharide, LPS, 100 mu g/mL). 4 h later bronchoalveolar lavage (BAL) was performed. The PDE inhibitors, rolipram (3 and 5 mg/kg) and theophylline ( 30 and 100 mg/kg) inhibited neutrophil recruitment, TNF-alpha release and c ellular activation in BAL. Salmeterol (0.5 mg/mL) and IL-10 (0.1 mu g) only inhibit TNF-alpha increase in the BAL fluid and db-AMPc (2.5 mu g/rat) was ineffective. The present data show that the selective PDE4 inhibitor, roli pram, and the non-selective PDE inhibitor, theophylline, markedly reduced t he pulmonary inflammation associated with acute lung injury in the rat. The se effects may be mediated in part by IL-10 rather than by cyclic AMP, as d emonstrated by the potent inhibitory activity of exogenous IL-10 on the inc rease in TNF-alpha release in BAL fluid of rats exposed to LPS. (C) Elsevie r, Paris.