Inhibitory action of spinorphin, an endogenous regulator of enkephalin-degrading enzymes, on carrageenan-induced polymorphonuclear neutrophil accumulation in mouse air-pouches.

Whether spinorphin, an endogenous regulator of enkephalin-degrading enzymes, plays a role in an anti-inflammatory action was examined, using a mouse air-pouch assay as a model of acute inflammation. Repeated intravenous administration (6 times) of spinorphin every hour significantly suppressed carrageenan-induced polymorphonuclear neutrophil (PMN) accumulation, an indicator of inflammation (3.21+/-0.95 x 10[6] cells vs 8.92+/-0.96 x 10[6] cells, 10mg/kg spinorphin-treated vs saline-treated group, n=5, P<0.01) at 6 hr. The combination of spinorphin and leuhistin (2 mg/kg, i.v.), a specific inhibitor of aminopeptidase N (APN), markedly suppressed the PMN accumulation induced by carrageenan (1.11+/-0.17 x 10[6] cells, 88% inhibition compared to the saline-treated group, n=5, P<0.01). This inhibition was less than, but comparable to that of dexamethasone (30 mg/kg/one shot, i. v.), a representative anti-inflammatory drug. These results indicate that spinorphin may be an endogenous anti-inflammatory regulator, its inhibitory activity being modulated by APN.