Immune Factor GM-CSF Significantly Improves Crohn's Disease Symptoms

Armen Hareyan's picture

Crohn's Disease Symptoms

Findings support new theory of mechanism behind inflammatory disorder

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 innate immune system. Because some of these disorders include symptoms virtually identical to those of Crohn's, they wondered if a similar process was occurring in Crohn's patients, with the excessive inflammatory response actually resulting from an unsuspected defect in innate immunity. To test this concept, they conducted a pilot study of treatment with GM-CSF, which stimulates the innate immune system and is usually used to restore bone marrow function in chemotherapy patients. Promising results from that study, published in 2002, led to the current multicenter investigation.

Patients with moderate to severe Crohn's disease enrolled in the study at 28 centers across the U.S. Of the 94 participants who completed the 56-day treatment cycle, 57 received daily injections of GM-CSF, while 37 received placebo injections. Participants were evaluated every two weeks during the study period and 30 days after treatment concluded. Based on a standard index of Crohn's disease symptoms, significantly more participants receiving GM-CSF were judged to have major improvement or remission of their symptoms than were those receiving placebo injections.

"We're encouraged that these results support this new understanding of Crohn's and hope they will lead to a new treatment option for the disease," says Korzenik, an assistant professor of Medicine at Harvard Medical School. "We're working with other institutions to conduct the larger-scale studies that would be needed to apply for FDA approval for this use of GM-CSF.

The study was supported by a grant from Berlex, Inc. which manufactures Leukine (sargramostim), the recombinant form of GM-CSF used in this research. The report's additional co-authors are John Valentine, MD, of the University of Florida, and Diana Hausman, MD, and Mark Gilbert, MD, of Berlex.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $450 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services. BOSTON - May 25, 2005