Special Reports and ReviewsInflammatory bowel disease: Etiology and pathogenesis☆,☆☆
Section snippets
Environmental factors
Among the many puzzles of IBD pathogenesis, one of the less understood and most difficult to tackle is the role of environmental factors in the appearance and progression of CD and UC in this century. Environmental factors are probably as important as the patient's genetic makeup for the risk of IBD. Potentially relevant environmental factors include prenatal events, breastfeeding, childhood infections, microbial agents, smoking, oral contraceptives, diet, hygiene, occupation, education,
Bacteria
An infectious etiology for IBD, with a direct cause-and-effect relationship between a single microorganism and inflammation, still remains plausible. The relationship between microbes and defined clinical entities is often ambiguous, but diseases of unknown etiology are unexpectedly proven to be infectious. The most striking example is peptic ulcer disease and Helicobacter pylori. Although traditional methods have failed to detect a specific pathogen associated with IBD, newer molecular
Mucosal B cells
When investigation switched from systemic immune events to those occurring in IBD-involved intestine, comparative mapping of B-cell distribution showed a massive increase in the number of plasma cells. This increase is not uniform with IgA, IgM, and IgG increasing 2-, 5-, and 30-fold, respectively.76 This pronounced humoral immune response is particularly striking for IgG, the antibody class with the highest pathogenic potential. The two forms of IBD can be distinguished based on this Ig's
Mimicking IBD: Animal models
In view of the experimental limitations imposed by studies of human disease, an animal model reproducing many, if not all, of the IBD characteristics would be extremely valuable. Early attempts to study experimental gut inflammation met with limited success. Spontaneous colonic lesions reported in the rat, mouse, gibbon, swine, and dog were sporadic, and the models were impractical. Allergic or hypersensitivity reactions induced colitis, as well as radiation, vitamin deficiency, lymphatic
Reasoning IBD: Realities and expectations
At the end of an intricate fiction book the reader expects to know “who did it,” but at the end of a review on the etiopathogenesis of IBD, the reader will not know “who did it.” The story on IBD is still unfolding, and outstanding questions prevent the final chapter from being written (Table 5).
Disease presentation Is CD a disease or a syndrome? Do other forms of IBD exist in addition to CD and UC? Environmental factors What environmental changes favor the
Acknowledgements
The author thanks Dr. Jeffry A. Katz for critical review of the manuscript.
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Address requests for reprints to: Claudio Fiocchi, M.D., Division of Gastroenterology, University Hospitals of Cleveland, Case Western Reserve University School of Medicine (BRB 425), 10900 Euclid Avenue, Cleveland, Ohio 44106-4952. Fax: (216) 368-1674.
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Supported by grants DK30399 and DK50984 from the National Institutes of Health and by the Crohn's & Colitis Foundation of America, Inc.