Immune factor GM-CSF significantly improves Crohn's disease symptoms

A drug that stimulates a specific part of the immune system may improve symptoms of Crohn's disease, according to a study in the May 26 New England Journal of Medicine. A multi-institutional research team reports that treatment with the growth factor GM-CSF significantly reduced symptom severity and improved quality of life after 56 days of daily drug injections. The finding supports a new concept that Crohn's, rather than being caused primarily by an excessive immune response, could actually result from defects in the body's first line of immune defense.

"We've proposed that the inflammation that occurs with Crohn's is actually secondary to an earlier problem," says Joshua Korzenik, MD, co-director of the Crohn's and Colitis Center at Massachusetts General Hospital (MGH), lead author of the NEJM study. "We believe there is a defect with the gastrointestinal innate immune system, a group of cells that stop any microbes from entering the body. If normal intestinal bacteria are not controlled by the innate immune system, a compensatory secondary inflammation could produce the symptoms of Crohn's."

Korzenik has been investigating this hypothesis for several years, in collaboration with Brian Dieckgraefe, MD, PhD, of the Gastroenterology Division at Washington University School of Medicine in St. Louis, a co-author of the current study.

A chronic inflammatory bowel disease, Crohn's usually affects the small intestine, causing abdominal pain and chronic diarrhea. Serious symptoms can include ulceration, bleeding, the development of fistulas openings from affected areas into other organs or intestinal blockage. About half a million people in the U.S.are affected by Crohn's. Current treatments are designed to reduce symptoms, and the disorder often enters periods of remission, some lengthy, before recurring.

Korzenik and Dieckgraefe developed their hypothesis based on studies of certain genetic disorders known to affect the innat

Contact: Sue McGreevey
Massachusetts General Hospital

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