Metallothionein: A Novel Therapeutic Target for Treatment of Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is a group of disorders characterized by chronic inflammation within the gastrointestinal tract. It is a multifactorial disease associated with immune-cell mediated oxidative damage to the intestinal mucosa. There is no cure for IBD, but anti-cytokine therapy can limit target inflammation and disease progression. Unfortunately, many patients are nonresponsive or develop resistance to anti-cytokine therapy over time creating a need for new therapeutic agents. Metallothionein (MT) is a small, highly conserved stress response protein that has been shown to modulate the immune response as a pro-inflammatory agent, regulates divalent heavy metal homeostasis, and acts as a reactive metabolite scavenger. Our research, as well as other groups studying MT, has described MT induction and release during IBD inflammatory stress response. The release of MT results in activation of inflammatory responses leading to progressive inflammation and subsequent expansion of MT synthesis. A monoclonal antibody specific for MT has been used in murine models of IBD and should only target the extracellular pool of MT, thus representing a novel therapeutic approach to this disease.

Keywords: Crohn's disease; Inflammatory bowel disease; Metallothionein; Ulcerative colitis; biologic therapy; inflammation..