Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities.
Ulcerative colitis (UC) and Crohn's disease (CD), the primary constituents of inflammatory bowel disease (IBD), are precipitated by a complex interaction of environmental, genetic, and immunoregulatory factors. Higher rates of IBD are seen in northern, industrialized countries, with greater prevalence among Caucasians and Ashkenazic Jews. Racial gaps are closing, indicating that environmental factors may play a role. IBD is multigenic, with the most clearly established genetic link between certain NOD2 variants and CD. Regardless of the underlying genetic predisposition, a growing body of data implicates a dysfunctional mucosal immune response to commensal bacteria in the pathogenesis of IBD, especially CD. Possible triggers include a chronic inflammatory response precipitated by infection with a particular pathogen or virus or a defective mucosal barrier. The characteristic inflammatory response begins with an infiltration of neutrophils and macrophages, which then release chemokines and cytokines. These in turn exacerbate the dysfunctional immune response and activate either TH1 or TH2 cells in the gut mucosa, respectively associated with CD and, less conclusively, with UC. Elucidation of immunological and genetic factors indicate multiple points at which the inflammatory cascade may be interrupted, yielding the possibility of precise, targeted therapies for IBD.
Hanauer
Stephen B
SB
Section of Gastroenterology, University of Chicago Medical Center, Chicago, Illinois 60637, USA. shanauer@uchicago.edu
D000818:Animals; D001424:Bacterial Infections / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation; D012307:Risk Factors