NEUTROPHIL ELASTASE INHIBITOR SUPPRESSES IL-17 BASED INFLAMMATION OF MURINE EXPERIMENTAL COLITIS

Abstract

[Background] Neutrophil elastase (NE) is a proteinase in granulocytes and plays an important role in the pathogenesis of inflammatory disorders. It has been reported that NE activity is elevated in both colonic mucosa and blood in inflammatory bowel disease (IBD) patients, and that it can act as an aggravating factor in IBD. To develop novel therapies for IBD, we examined the effects of an NE inhibitor, Elaspor^®, on murine experimental colitis. [Methods] Acute colitis was induced in BALB/c mice by administration of dextran sulfate sodium (DSS) in drinking water for 7 days. NE inhibitor was administered subcutaneously to mice prior to and during the induction of colitis. Disease activity index (DAI), colonic myeloperoxidase (MPO) activity, luminal NE activity, and mRNA expression in the colon were then investigated. [Results] Subcutaneous administration of NE inhibitor ameliorated the severity of DSS-induced colitis. NE activity was elevated in inflamed colon, and was reduced by NE inhibitor administration. mRNA expression levels of IL-17, a Th17-based inflammatory factor, was also decreased in the colon of NE inhibitor-administered mice. [Conclusion] These results suggest that NE inhibitor ameliorated colonic inflammation by decreasing both the activity of NE and the effects of cytokine balance. Clinically, NE inhibitor improves injuries associated with systemic inflammatory response syndrome. Similarly, clinical use of this inhibitor would further clarify its usefulness in clinical colonic inflammation.