Title:Adrenomedullin as a Potential Therapeutic Agent for Inflammatory Bowel Disease
Volume: 14
Issue: 4
Author(s): Shinya Ashizuka, Haruhiko Inatsu, Kyoko Inagaki-Ohara, Toshihiro Kita and Kazuo Kitamura
Affiliation:
Keywords:
Adrenomedullin, anti-inflammatory action, inflammatory bowel disease, inflammatory cytokines, translational research,
ulcerative colitis.
Abstract: Adrenomedullin (AM) was originally isolated from human pheochromocytoma as a biologically active peptide
with potent vasodilating action but is now known to exert a wide range of physiological effects, including cardiovascular
protection, neovascularization, and apoptosis suppression. A variety of tissues, including the gastrointestinal tract, have
been shown to constitutively produce AM. Pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-1,
and lipopolysaccharides, induce the production and secretion of AM. Conversely, AM induces the downregulation of inflammatory
cytokines in cultured cells. Furthermore, AM downregulates inflammatory processes in a variety of different
colitis models, including acetic acid-induced colitis and dextran sulfate sodium-induced colitis. AM exerts antiinflammatory
and antibacterial effects and stimulates mucosal regeneration for the maintenance of the colonic epithelial
barrier. Here, we describe the first use of AM to treat patients with refractory ulcerative colitis. The results strongly suggest
that AM has potential as a new therapeutic agent for the treatment of refractory ulcerative colitis.
