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From the Institute of Pharmacology,*
University of
Messina, Messina, Italy; the William Harvey Research
Institute,
St. Bartholomew’s, and the Royal
London School of Medicine and Dentistry, Charterhouse Square, London,
United Kingdom; and the Department of
Biomorphology,
School of Medicine, the
Department of Veterinary Medicine and
Pharmacology,§
and the Institute of Veterinary
General Pathology and Pathological Anatomy,
University of Messina, Messina, Italy
There is limited evidence that inhibition of the activity of the protease calpain I reduces inflammation. Here we investigate the effects of calpain inhibitor I in animal models of acute and chronic inflammation (carrageenan-induced pleurisy and collagen-induced arthritis). We report here for the first 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) exerts potent anti-inflammatory effects (eg, inhibition of pleural exudate formation, mononuclear cell infiltration, delayed the development of the clinical signs and histological injury) in vivo. Furthermore, calpain inhibitor I reduced (1) the staining for nitrotyrosine and poly (ADP-ribose) polymerase (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. Inhibition of calpain I activity may represent a novel therapeutic approach for the therapy of inflammation.
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