March 28, 2001 - Study Identifies Culprits in Food Allergy Inflammation
CINCINNATI -- A Children's Hospital Medical Center of Cincinnati study has definitively linked a type of food allergy whose occurrences have risen dramatically in recent years to eosinophils, a type of cell usually found in the blood.
When an allergen is ingested, eosinophils invade tissue in the gastrointestinal tract, causing difficulty in moving food through the gastrointestinal system, enlargement of the stomach, and failure to thrive, according to Marc E. Rothenberg, M.D., Ph.D., the study's senior author. The study, published in the April issue of Nature Immunology, lays the foundation for the development of new drugs that block this critical food allergy pathway.
"Allergies do affect the G-I tract; they're serious, and eosinophils are the culprits," says Dr. Rothenberg. "Oral antigens -- foods that people are allergic to -- induce eosinophilic inflammation in various segments of the gastrointestinal tract, including the esophagus, stomach and small intestine.
"This disease process is governed by and dependent upon eotaxin, which plays a major role in the body's response to allergens and recruits eosinophils into inflammatory tissue. This paper proves that it is the eosinophils that cause allergic inflammation in the G-I tract.", says Dr. Rothenberg.
The study involved the first experimental system, one that Dr. Rothenberg's lab developed, to analyze complex food allergies not related to anaphylaxis (an exaggerated allergic reaction), such as allergic reactions to peanuts. Dr. Rothenberg and Simon Hogan, Ph.D., 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, stomach, small intestine and esophagus, and induced disease with many features of human disease, including T-cell activation (increased levels of interleukin-4 and interleukin-5), and B-cell responses (IgE antibodies), which are molecules associated with allergy. In those mice genetically engineered without eotaxin, however, eosinophil recruitment into the small intestine was eliminated.
"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 allergy in the gut," says Dr. Rothenberg.
Allergic diseases have reached epidemic proportions, inflicting nearly 30 percent of the population of most countries throughout the world, according to Dr. Rothenberg, section chief of allergy and clinical immunology in Cincinnati Children's division of pulmonary medicine, allergy and clinical immunology.
The study was supported in part by grants from the National Institutes of Health and by the Human Frontier Science Program.
Contact Information
Jim Feuer (jfeuer@chmcc.org), 513-636-4420
