Calpain inhibitor I reduces the development of acute and chronic inflammation

There is limited evidence that inhibition of the activity of the protease c alpain I reduces inflammation. Here we investigate the effects of calpain i nhibitor I in animal models of acute and chronic inflammation (carrageenan- induced pleurisy and collagen-induced arthritis). We report here for the fi rst time that calpain inhibitor I (given at 5, 10, or 20 mg/kg i.p. in the pleurisy model or at 5 mg/kg i.p every 48 hours in the arthritis model) exe rts potent anti-inflammatory effects (eg, inhibition of pleural exudate for mation, mononuclear cell infiltration, delayed the development of the clini cal signs and histological injury) in vivo. Furthermore, calpain inhibitor I reduced (1) the staining for nitrotyrosine and poly (ADP-ribose) polymera se (immunohistochemistry) and (2) the expression of inducible nitric oxide synthase and cyclooxygenase-2 in the lungs of carrageenan-treated rats and in joints from collagen-treated rats. Thus, prevention of the activation of calpain I reduces the development of acute and chronic inflammation. Inhib ition of calpain I activity may represent a novel therapeutic approach for the therapy of inflammation.