Adrenomedullin as a Potential Therapeutic Agent for Refractory Ulcerative Colitis

K. Kitamura , M.D., Ph.D. (*) • S. Ashizuka • H. Inatsu • T. Kita Department of Internal Medicine, Circulatory and Body Fluid Regulation, Faculty of Medicine , University of Miyazaki , 5200 Kihara, Kiyotake , Miyazaki City , Miyazaki 889-1692 , Japan e-mail: [email protected] Abstract Adrenomedullin (AM) was originally isolated from human pheochromocytoma as a biologically active peptide with potent vasodilating action, but it also has a wide range of physiological properties including cardiovascular protection, neovascularization, and the ability to suppress apoptosis. It is constitutively produced by various tissues including the gastrointestinal tract. AM production and secretion can be induced by pro-infl ammatory cytokines such as tumor necrosis factor-α and interleukin-1, as well as by lipopolysaccharide. Conversely, AM causes the downregulation of infl ammatory cytokines in cultured cells and downregulates inflammatory processes in various models of colitis, including those induced by acetic acid and by dextran sulfate sodium. AM works by exerting anti-infl ammatory and antibacterial effects and by stimulating mucosal regeneration and supporting maintenance of the colonic epithelial barrier. The present fi ndings suggest that AM could serve as a novel agent for treating refractory ulcerative colitis.