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Allergy More Likely In Clean Environments - Duke Researchers Compared Lab Mice and Rats to Wild Rodents - Good Hygiene Causes Allergies

June 20th 2006

Allergy More Likely In Clean Environments - Duke Researchers Compared Lab Mice and Rats to Wild Rodents - Good Hygiene Causes Allergies

Wild Rodents

Duke University researchers say countries that are “overly” hygienic have a tendency to acquire autoimmune disease and allergic reactions.  Their research involved a comparison between wild mice and common rats to laboratory mice and rats. 

The researchers focused on the animal’s production of various antibodies, known as immunoglobulins, either associated with autoimmune disease or associated with allergy.  When the mice, rats, or humans for that matter, encounter an invader or antigen, their immune systems kick into action producing antibodies that bind to the invader and destroy it. 

According to William Parker, PhD, there are many classes of immunoglobulins (Ig).  Parker is an assistant professor of experimental surgery and senior member of the study team. 


The IgG type of immunoglobulins is often involved in autoimmune disease, while the IgE type is likely a key defender against parasites and has been implicated in allergic reactions in humans.

The researchers went out and trapped wild rats in rural and urban settings in North Carolina.  They then trapped wild mice in Wisconsin. They measured the levels of antibodies in the blood of the wild rodents and compared the levels to those levels observed in mice and rats housed in the Duke animal facilities.

Parker said "Laboratory rodents live in a virtually germ- and parasite-free environment, and they receive extensive medical care - conditions that are comparable to what humans living in Westernized, hygienic societies experience.  On the other hand, rodents living in the wild are exposed to a wide variety of microbes and parasites, much like humans living in societies without modern health care and where hygiene is harder to maintain."


Parker and his team found that the wild rodents had higher levels of IgG and IgE, with the IgE showing the most pronounced difference.  Additionally, the wild rodents had higher levels of a particular type of IgG called polyreactive, autoreactive IgG, which is associated with autoimmune disease in hygienic humans and rodents.  Interestingly, increased levels of these antibodies did not presumably cause “untoward” reactions in the wild rodents, Parker said.

The wild rodents had higher levels of IgE as expected, since these rodents would likely have encountered parasites that activated the production of antibodies as protection.  What was unexpected was the discovery that the wild rodents produced polyreactive, autoreactive IgG.  Polyreactive, autoreactive antibodies are always found to be a type of IgM, a different type of antibody than IgG, although all previous studies have focused on hygienic populations.


"These results appear to demonstrate that the environment has profound effects on the production of IgE and autoreactive IgG," Parker said. "While the production of these two antibody types lead to autoimmune disease and allergy, respectively, in the laboratory animals, their production seemed to represent a nonpathogenic, protective response to the environment by the wild rodents.

"We would expect that the targets of the autoreactive IgG and IgE in the 'hygienic' laboratory rodents would be substantially different from the targets of the same antibodies in the wild animals," he said.

In the wild animals, the autoreactive IgG likely bind to environmental antigens and therefore do not have deleterious effects, Parker said.

"However, autoreactive IgG in hygienic animals can bind avidly to the body's own cells, which can lead to autoimmune disease," he said. "In a parallel fashion, the IgE in the wild animals is protective because the antibodies bind to parasite antigens, while the same antibodies in laboratory animals would bind to abundant but harmless environmental antigens, leading to allergies to those antigens."

"These results are consistent with the idea that animals without access to modern medicine have high levels of autoimmune-like and allergic-like immune responses that represent appropriate responses to unknown factors in their environment," he said.

"The most commonly accepted explanation for this high incidence of allergy and perhaps autoimmune disease is the hygiene hypothesis," Parker said. He says this hypothesis has not been thoroughly tested in animal studies, and the few studies conducted have focused on specific pathogens or parasites.

There are up to 50 million Americans who suffer from allergies, and another 8 million who have autoimmune disorders, including lupus, insulin-dependant diabetes, rheumatoid arthritis and scleroderma.  The research is published in the online edition of the Scandinavian Journal of Immunology. The research was supported by the National Institutes of Health, the Duke University School of Medicine and the Fannie E. Rippel Foundation.

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