Modulation of inflammatory paw oedema by cysteamine in the rat

Cysteamine, a potent somatostatin depletor, was used in the present study to investigate the role of endogenous somatostatin in acute peripheral inflammation. The acute inflammation was induced by intraplantar injection of carrageenan (1%), histamine (5 micromol), or formalin (2.5%) in the rat hind paw. The induced inflammation and the formation of oedema were determined by measurement of the paw thickness. Given subcutaneously (s.c.) 1 h before carrageenan, cysteamine caused significant, dose-dependent and long-lasting inhibition of rat paw oedema induced by carrageenan. At doses of 12.5, 25, 50 or 100 mg kg (-1), cysteamine significantly inhibited the carrageenan-induced paw oedema at 4 h by 52.3, 40, 40.7 or 26.3%. Cysteamine given at 300 mg kg (-1), a dose well known to deplete tissue somatostatin, reduced oedema by only 16.2% vs control values. Significant inhibition of the carrageenan-induced rat paw oedema was still evident 24 h post-injection at cysteamine doses of 12.5, 25, 50 or 100 mg kg (-1). Given s.c. at 300 mg kg (-1), 4 h prior to carrageenan, cysteamine decreased rat paw oedema at 4 h by 14.9%. Cysteamine (300 mg kg (-1)), 4 h beforehand, had little modulatory effect on the oedema induced by formalin (2.5%) but reduced that caused by intraplantar histamine (5 micromol). The anti-oedematogenic effect of indomethacin, but not that of the selective COX-2 inhibitor celecoxib, was less marked in rats pre-treated with cysteamine at 300 mg kg (-1). Cysteamine (0.3 microg- 0.3 mg paw (-1)) co-administered with carrageenan was devoid of anti-inflammatory effect and even promoted inflammation at low concentrations. Cysteamine given locally alone induced slight paw oedema. These data indicate that systemic cysteamine possesses potent and long-lasting anti-inflammatory effects and modulates the anti-inflammatory effect of cyclooxygenase inhibitors in a model of peripheral inflammation in the rat. The effect of cysteamine is likely to be mediated via central action.