Effect of FK506 (tacrolimus) in animal models of inflammation.

Inflammation is the response of living tissue to damage. Cytokines play an important role in inflammatory processes. FK506 (tacrolimus), an immunosuppressant, is known to reduce the activation of microglia in vitro and affect the expression of various cytokines like interleukin-1, interleukin-6 and tumor necrosis factor. With this background the present study was designed to explore the effect of FK506 in animal models of acute inflammation and experimental pleurisy. Acute inflammation in rats was induced by intraplantar injection of carrageenan (1%, w/v). Experimental pleurisy was induced in rats by intrapleural injection of carrageenan (2%, w/v). Pretreatment with FK506 (0.5-3 mg/kg p.o.) significantly and dose-dependently reduced carrageenan-induced increase in paw volume, as well as carrageenan-induced inflammatory nociception. FK506 (1 and 3 mg/kg p.o.) inhibits exudate formation and migration of polymorhonuclear leukocytes and monocytes in carrageenan-induced experimental pleurisy. The myeloperoxidase enzyme level was significantly increased in carrageenan-treated animals, which was significantly reversed by FK506 treatment. The results of the present study suggest the potential anti-inflammatory properties of FK506 against carrageenan-induced acute inflammation and experimental pleurisy.