The anti-inflammatory effects of the phosphodiesterase inhibitor pentoxifylline in the rat

The present study aimed to evaluate the anti-inflammatory effects of pentoxifylline (PTX). a non-specific phosphodiesterase inhibitor in the rat. Acute inflammation was induced by subplantar injection of carrageenan (1%) in the rat hind paw. Results showed that intraperitoneal (i.p.) administration of PTX (36 or 72 mg kg(-1)) 30 min prior to carrageenan reduced the paw oedema response in dose-dependent manner with a maximal effect of 18.9 and 40.1%. respectively, at 2 h post-carrageenan (P < 0.001 and <0.001 at respective doses). Theophylline given at equimolar doses (29.9 or 45.8 mg kg(-1), i.p.) did not reduce the oedema response. With higher doses of PTX (144-300 mg kg(-1), the anti-oedema effect of the drug was more pronounced, but mainly confined to the first 2 h following carrageenan injection and decreasing rapidly thereafter, PTX (72 mg kg(-1) i.p.) given 30 min after carrageenan challenge reduced the oedema response by 24.7 and 26.2% at 1 and 2 h after dosing (P < 0.05 and <0.05. respectively). PTX (36 or 72 mg kg(-1) i.p.) co-administered with indomethacin (5 mg kg(-1), i.p.) 30 min before carrageenan had little modulatory effect on the anti-oedema effect of indomethacin, but the higher dose of PTX (144 mg kg(-1), i.p.) reduced the anti-inflammatory effect of indomethacin by 24% at 4 h post-carrageenan. PTX (72 mg kg(-1). i.p.) enhanced the anti-oedema effect of the selective COX-2 inhibitor celecoxib (33 mg kg(-1) i.p.) by 55.1% at 4 h post-carrageenan. In contrast. the higher dose of PTX (144 mg kg(-1) i.p.) reduced the anti-oedema effect of celecoxib by 46.8% at 4 h post-carrageenan. PTX (36 or 72 mg kg(-1)) enhanced the anti-oedema effect of dexamethasone (0.1 mg kg(-1)) with maximal effect of 76 and 104.8% at 2 h post-carrageenan (P < 0.01 and <0.01 for respective doses). PTX (0.6 mg per paw) given with carrageenan into the rat hind paw reduced the oedema response with a maximal effect of 33.4% at 1 h following carrageenan, PTX (0.6 mg per paw) given in the contralateral hind paw reduced the carrageenan-induced paw oedema for 1 h by 32.2%. Thus, PTX. when given at doses comparable to those used in man for treatment of circulatory disorders displayed anti-inflammatory in vivo and enhanced the anti-inflammatory effect of a selective COX-2 inhibitor or dexamethasone. PTX may have therapeutic potential as anti-inflammatory agent either alone or in combination with non-steroidal anti-inflammatory drugs or with steroids. There is also an intriguing possibility for the use of topical preparations, for the management of local inflammatory conditions. (C) 2003 Elsevier Science Ltd. All rights reserved.