Rodent Comparison Supports Hygiene Hypothesis

A study appearing in the Scandinavian Journal of Immunology lends support to the idea that too much cleanliness can be bad for you. The results may explain why people in industrialized societies that practice high standards of hygiene have higher rates of allergy and autoimmune diseases than do people in less developed societies in which hygiene is harder to achieve.

The “hygiene hypothesis,” is based around the idea that people in hygienic societies have not had their immune systems challenged during everyday life by the host of microbes commonly found in the environment. In the new study, Duke University Medical Center researchers compared wild rodents with their laboratory counterparts by measuring specific immune system responses.

“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,” said Duke’s William Parker, senior member of the study team. “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 explained that up to 50 million Americans suffer from allergies, and another 8 million have some form of autoimmune disorder, which occurs when an overactive immune system attacks tissues in the body. “The most commonly accepted explanation for this high incidence of allergy and perhaps autoimmune disease is the hygiene hypothesis,” said Parker. But up until now, this hypothesis has not been thoroughly tested in animal studies.

In comparing the immune systems of wild house mice and common rats to laboratory mice and rats, the team focused on the production of various antibodies, known as immunoglobulins, either associated with autoimmune disease or associated with allergy. Of the many classes of immunoglobulins (Ig), the IgG type 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 results showed that all of 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. However, the increased levels of these antibodies did not presumably cause untoward reactions in the wild rodents, Parker said.

The higher levels of IgE in the wild rodents was not unexpected, said Parker, since wild rodents would likely have encountered parasites that activated the production of antibodies as protection. However, the production of polyreactive, autoreactive IgG by the wild rodents was unexpected: 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 explained. “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. 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,” Parker said.

While this study suggests that the environment plays an important role in how the immune systems in animals develop, genetics is likely to be involved as well, according to Parker. He now is planning additional studies to help decipher the full role of genetics.

Source: Duke University Medical Center

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