Review article: anti-tryptase therapy in inflammatory bowel disease

A number of studies have shown that activated mast cells are involved in the pathogenesis of inflammatory and allergic diseases. Tryptase is one of the serine proteases that stored almost exclusively in the secretory granules of mast cells. It acts to induce microvascular leakage, the chemotaxis of inflammatory cells, and stimulates the release of inflammatory cytokines through the mitogen-activated protein kinase/activator protein-1 pathway and protease-activated receptor (PAR) nuclear factor-kappa B pathway. Recent studies have strongly indicated that tryptase and PAR are implicated in the pathogenesis of inflammatory bowel disease and experimental colitis. The effect of anti-tryptase therapy on human inflammatory bowel disease and experimental colitis has been demonstrated. The result of a pilot study has revealed that systemic administration of a specific tryptase inhibitor is safe and there is evidence of activity in the treatment of ulcerative colitis. Recently, we found that nafamostat mesilate, which selectively inhibits tryptase activity at low concentration, could reduce intestinal inflammation in rats. In addition, nafamostat mesilate enema improved clinical and endoscopic findings in ulcerative colitis patients, resistant to conventional therapy such as corticosteroids and sulfasalazine/5-aminosalicylic acid. These studies suggest that anti-tryptase therapy may represent a new therapeutic strategy for human inflammatory bowel disease.