Cincinnati Children's Researchers Uncover Critical Food Allergy Pathway

The discovery, to be published in the June 6 edition of Proceedings of the National Academy of Sciences (PNAS), could lead rapidly to clinical trials of new drugs that would block the protein eotaxin, thereby preventing allergic reactions in the gastrointestinal tract, according to Marc E. Rothenberg, M.D., Ph.D, the study's senior author.

In the PNAS study, Dr. Rothenberg and lead author Simon P. Hogan, Ph.D., developed the first experimental system to analyze complex food allergies not related to anaphylaxis (an exaggerated allergic reaction), such as allergic reactions to peanuts. They found that the inflammatory response involved in allergic intestinal inflammation is governed by eotaxin.

Eotaxin belongs to a family of molecules called chemokines, which play a major role in the body's response to allergens. Eotaxin acts to recruit eosinophils, a type of cell normally found in the blood, into inflammatory tissue.

Drs. Rothenberg and Hogan developed a mouse model of eosinophil-associated gastrointestinal allergy and challenged the mice with oral allergens, mimicking food. This resulted in eosinophil accumulation in the blood and small intestine. In those mice genetically engineered without eotaxin, however, eosinophil recruitment into the small intestine was eliminated, while accumulation in the blood was enhanced.

"This demonstrates a critical role for eotaxin specifically in regulating allergic responses in the gastrointestinal tract," says Dr. Rothenberg. "Since agents that block eotaxin and similar chemokines are being actively developed by a number of pharmaceutical companies, these studies provide impetus for rapidly applying these new drugs to gut allergy."

Allergic diseases have reached epidemic proportions, inflicting nearly 30 percent of the population of most countries throughout the world, according to Dr. Rothenberg. "We have not only seen a marked increase in the incidence of allergic diseases (a doubling in recent decades), but the emergence of allergic reactions to common environmental substances has also increased at an alarming rate," says Dr. Rothenberg, section chief of allergy and clinical immunology in Cincinnati Children's division of pulmonary medicine, allergy and clinical immunology.

"For example," he says, "food allergies such as peanut anaphylaxis now affect about 5% of the population. These problems are particularly concerning at young ages when adverse reactions to new foods in the diets often becomes a challenging problem."

Because of the rise in food allergies and their associated reactions, Cincinnati's Children's has launched a new Food Allergy Program that will serve as an international referral center for food allergy and eosinophilic disorders.

As part of the program, allergists, gastroenterologists, nurses, and nutritionists take a comprehensive approach to solve the complex medical issues associated with adverse reactions to foods. The new program not only provides outstanding medical care but also conducts significant research designed to understand how and why allergic responses occur.

Dr. Rothenberg is a leading scientist in the area of eosinophilic disorders. He has published extensively on molecular mechanisms of allergic responses, including an article in The New England Journal of Medicine titled Eosinophilia. He has earned numerous international awards, including the prestigious Pharmacia Allergy Research Foundation International Award for 1998.

Dr. Rothenberg's other awards include the Young Investigator Award and the Scholar in Allergy Award from the American Academy of Allergy, Asthma, and Immunology. He recently received the annual grant from the International Life Style Institute for Food Allergy Research to further these studies. He joined Cincinnati Children's in 1996 from Harvard Medical School.