Mouse Model Of Food Allergies Reveals Cause Of Inflammation

The research identifies the culprits as eosinophils, immune cells packed with powerful proteins that, when released, destroy surrounding tissues and help rally other immune cells to sites of infection. Eosinophils often appear in high numbers at sites of allergic inflammation, but researchers have not known if the cells caused the disease or were merely bystanders called to the scene.

"This study provides very clear evidence that, in this model, eosinophils play a critical role in disease," says Marshall Plaut, M.D., chief of the allergic mechanisms section at the National Institute of Allergy and Infectious Diseases (NIAID), which funded the study. "Understanding how and why these cells attack the digestive organs is an important step toward understanding a number of human gastrointestinal inflammatory diseases, including food allergy."

In most of us, our immune system ignores the foods we eat. If our defenses stop ignoring these foods, however, immune cells can rush to the digestive tract and launch an attack, leading to allergies. Marc Rothenberg, M.D., Ph.D., of Children's Hospital Medical Center in Cincinnati, directed a research team to discover why that happens. They developed a mouse model of eosinophilic gastrointestinal inflammatory diseases, which lead to weight loss, enlarged or inflamed digestive tissues, and the inability of food to move properly through the digestive tract.

To produce a food allergy in mice, lead author Simon Hogan, Ph.D., and colleagues first injected the animals with small amounts of ovalbumin, a harmless protein found in eggs. The injections sensitized the mice to the protein, putting their immune systems on alert for future exposures. The researchers then fed the animals specially coated ovalbumin pellets, which were designed to survive the acidic environment of the stomach. When the food moved from the stomach into the small intestine it triggered an allergic reaction. "The response to the egg protein in mice resembled inflammatory food allergies in humans, providing us with a good system for understanding these diseases," says Dr. Rothenberg.

The animals became ill and lost weight as multiple regions of their digestive tracts became inflamed. Immune system proteins and cells rushed to the affected areas, and eosinophils accumulated in high numbers, particularly around damaged nerve cells. The walls of digestive organs swelled and food became stalled in the stomach; both of these findings are characteristic of human eosinophilic gastrointestinal inflammation.

To see if eosinophils were in part responsible for the allergy symptoms, the researchers studied a protein called eotaxin, which plays a role in some respiratory allergies. Eotaxin is a type of chemical distress call that summons eosinophils when the body senses danger. The Rothenberg team discovered that, in the sensitized mice, ovalbumin caused some of the cells lining the digestive tract to release eotaxin and attract eosinophils to the site. When the researchers repeated the experiment in mice that lacked the eotaxin gene, eosinophils did not appear and the mice did not develop the severe symptoms seen in normal mice.

"This provides strong evidence that eosinophils are key players in food allergies," explains Dr. Rothenberg. "A food can trigger eotaxin, which attracts eosinophils to the site, which in turn attack healthy tissue and cause disease, perhaps by damaging the nerve cells that communicate with the digestive tract."

By identifying eosinophils as a major cause of digestive inflammation, Dr. Rothenberg hopes to find new options for treating the disease. He points out that several anti-eosinophil drugs are undergoing clinical trials for other diseases, and these might be effective agents to treat some food allergies. In addition, his mouse model of food-induced digestive illnesses should allow researchers to more thoroughly study related diseases and advance our knowledge of food sensitivities and allergies.

NIAID is a component of the National Institutes of Health (NIH). NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

Reference: Hogan SP et al. A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation. Nature Immunology 2:353-60 (2001).

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