Pathophysiology of and New Treatment for Ulcerative Colitis

Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease affecting the mucosa of the colon and rectum. The inflammation seen with UC is an acute-on-chronic type with marked infiltration of lymphocytes, plasma cells, neutrophils, and macrophages induced by interleukin-8 (IL-8) and other cytokines. There was a significant correlation between IL-8 and myeloperoxidase levels in the colonic mucosa of UC tissue. Activated platelets were involved in increased production of reactive oxygen metabolites released from neutrophils, soluble phospholipase II, and platelet microparticles. Cytokine balance, which consists of proinflammatory and immunosuppressive cytokines, is important for provoking the mucosal inflammation. In UC, production of proinflammatory cytokines such as IL-1β, IL-6, IL-8, and tumor necrosis fector-α in the colonic mucosa was more increased than that of immunosuppressive cytokines such as IL-10, transforming growth factor-β, and interleukin-1 receptor antagonist. The number of CD45RO+CD4+ and CD45RO+CD8+ T cells expressing Fas ligands in UC mucosa was significantly increased compared to that in the controls. We succeeded in establishing an experimental ulcerative colitis model in mice (MAIDS colitis). A double color-staining immunofluorescence study showed that Mac-1 cells were positive for interferon-γ (IFNγ) or IL-10 (or both), and CD4 T cells were positive for IL-10. The susceptible genes for inflammatory bowel disease are being assessed. The carriage ratio of allele K in codon 469 of ICAM-1 and allele A6 of MICA was higher in UC than the controls. There are three kinds of leukocytapheresis for treatment of UC: the leukocyte removal filter method, centrifugal leukocyte apheresis, and granulocyte apheresis (G-column). These treatments were effective for 60%–70% of patients with steroid-resistant and steroid-dependent UC.