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Am J Pathol. 2000 Dec;157(6):2065-79.

Calpain inhibitor I reduces the development of acute and chronic inflammation.

Author information

1
Institute of Pharmacology, University of Messina, Messina, Italy. St. Bartholomew's, and the Royal London School of Medicine and Dentistry, Charterhouse Square, London, United Kingdom. salvator@www.unime.it

Abstract

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.

PMID:
11106579
PMCID:
PMC1885785
DOI:
10.1016/S0002-9440(10)64845-6
[Indexed for MEDLINE]
Free PMC Article

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