Inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) are common and vexing problems. The causes and triggers for these conditions remain unclear, and consistently effective treatment continues to be elusive. Ulcerative colitis and Crohn’s disease are two types of chronic inflammation affecting the gastrointestinal tract, and sometimes their symptoms and other features overlap. Familial clustering and genetic factors also appear to be involved.

Patients affected with these diseases often undergo a long course of intermittent relapses and remissions, greatly diminishing their quality of life. In most cases, patients are required to take long-term medications to keep a potential relapse in check. Bleeding and stricture formation leading to obstruction and perforation are complications of the continuous inflammatory process. In some cases, repeated operations are required to treat complications. Patients with ulcerative colitis may eventually face removal of the colon, which usually cures the disease but may create other significant health issues. However, for patients with Crohn’s disease, which can affect any segment of the gastrointestinal tract, surgery is seldom curative. In both cases, chronic inflammation can lead to the development of cancer.

New discoveries in chronic inflammatory bowel diseases have moved researchers closer to identifying the genes and mutations responsible for predisposition and perpetuation of chronic intestinal inflammation. In addition, careful examination of single nucleotide polymorphism suggests that it is possible to predict the absence or presence of the disease, the biological behavior or phenotype of the disease (e.g. fibrostenosing or fistulizing Crohn’s disease), successful response to medical treatment (steroids, azothiaprine) or surgery, and long-term prognosis.

At UW Medicine, researchers are planning to create a database of patients suffering from chronic inflammatory bowel diseases and attempt to match the risk factors and the clinical features with detailed and serial DNA micro-array analysis. Researchers also plan to include a unique population of patients whose disease is diagnosed for the first time and therefore the cellular and the genetic expression of inflammation will not be complicated by drug treatment, infection, or the trauma of surgery.

Faculty members in the Division of Gastroenterology are also investigating the progression of chronic inflammation from metaplasia to dysplasia, and finally to neoplasia. The aim is to understand this multi-step sequential change and to determine the optimal time to intervene to prevent cancer formation. At the same time, randomized, controlled, clinical trials are being performed to examine the use of simple, safe, oral medications to halt the progression of chronic inflammation.

Understanding the genetic background at the cellular and molecular level affords the great opportunity of solving the factors predisposing a person to inflammatory bowel diseases. Studying the genetic changes of various cellular and biochemical changes, including cytokine profiles and their gene expressions makes it possible to identify the environmental factors that trigger the inflammatory process. These approaches, when combined with the analysis of the cell cycle kinetics and the molecular markers of cell growth and differentiation, will enable UW scientists to pinpoint the causes and progression of inflammation, cytokine production, and tissue reaction. Researchers can then correlate these with the phenotypic features of our patients.

UW Medicine investigators are among the vanguard of those conducting new clinical trials using biological agents (not traditional immunosuppressants) for the treatment of chronic inflammatory bowel disease during relapse. There are substantial numbers of sufferers of chronic inflammatory bowel diseases in the Pacific Northwest, yet there is no organized and concerted effort to push research forward, educate patients and the public, and coordinate effective treatment and clinical trials in a single research center. Similar centers exist on the East Coast (Philadelphia, Boston, New York), Midwest (Chicago), the Southwest (Dallas, Houston) and the Pacific West (Los Angeles, San Francisco). The Division of Gastroenterology at UW Medicine is equipped to meet the challenge, taking responsibility for leading a multi-disciplinary approach to research in chronic inflammatory bowel disease in the Pacific Northwest, and contributing to the national effort to advance research and treatment.

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