EFFECTS OF CANNABINOID RECEPTOR LIGANDS ON LPS-INDUCED PULMONARY INFLAMMATION IN MICE

The effects of cannabinoid receptor agonists WIN 55,212-2, Delta 9-tet rahydrocannabinol (Delta 9-THC), arachidonoylethanolamide :anandamide) and palmitoylethanolamide on lipopolysaccharide (LPS) -induced bronch opulmonary inflammation in mice were investigated.WIN 55,212-2 and Del ta 9-THC induced a concentration-depend ent decrease in TNF-alpha leve l in the bronchoalveolar lavage fluid (BALF) (maximum inhibition 52.7% and 36.9% for intranasal doses of 750 nmol.kg(-1) and 2.65 mmol.kg(-1 ), respectively). This effect was accompanied by moderately reduced ne utrophil recruitment. Palmitoylethanolamide (750 nmol.kg(-1)) diminish ed the level of TNF-alpha in BALF by 31.5% but had no effect on neutro phil recruitment. Anandamide (7.5-750 nmol.kg(-1)) did not influence t he inflammatory process but TNF-alpha level and neutrophil recruitment were decreased by 28.0% and 62.0%, respectively, with 0.075 nmol.kg(- 1). These results demonstrate that the cannabinoid receptor ligands in hibited LPS-induced pulmonary inflammation and suggest that this effec t could be at least in part mediated by the cannabinoid CB2 receptor. (C) 1998 Elsevier Science Inc.