Bacterial Infections Alter Allergic Response

Findings Support Hygiene Hypothesis

Researchers at National Jewish Medical and Research Center have gathered strong experimental support for the hygiene hypothesis, a proposed explanation for the worldwide rise in asthma and allergies. The research team, led by Richard Martin, M.D., found that early infection with the bacterium Mycoplasma pneumoniae reduced a mouse’s subsequent response to allergens. Alternatively, mice exposed to allergens prior to infection, developed a stronger allergic response. The research team is reporting its results in the March 2003 issue of the journal Infection and Immunity.

“For the first time, we have shown that a bacterial infection can modify the allergic response,” said Dr. Martin, Vice Chair of the Department of Medicine at National Jewish. “Timing is everything, however. Our results suggest that M. pneumoniae, or a related pathogen, could help prevent asthma and other allergic diseases, but only if the infection occurs before a person is sensitized to an allergen.”

Asthma and allergies have both been on the rise for several decades, especially in developed countries. The hygiene hypothesis has offered one explanation for this increase: compared with the past, children living in these countries today are exposed to fewer infectious organisms, which are necessary to properly train their developing immune systems. As a result, their immune systems overreact to relatively harmless irritants, leading to allergies and asthma.

So far, however, most evidence both for and against the hygiene hypothesis has been indirect and observational. The National Jewish research team sought more direct evidence using a mouse model of asthma and the bacterium M. pneumoniae, a common cause of community-acquired pneumonia.

In their study, Martin and his colleagues inoculated mice with either the bacterium or with a saline solution. Then all the mice were made allergic to the egg protein ovalbumin. Two weeks later, the mice were then exposed to the ovalbumin again, and their allergic response was evaluated.

On several measures, the mice that had been infected showed a milder reaction to the ovalbumin than did the control mice. Bronchial hyperresponsiveness (a measure of the “twitchiness” of the airways of these asthma-prone mice), levels of the cytokine IL-4, and total white cell count in the airways were all lower in the previously infected mice than in mice who were not infected. Levels of gamma interferon, which is associated with a healthy non-allergic immune response, were higher in the previously infected mice.

When mice were first sensitized and exposed to ovalbumin, then infected with bacteria, they showed greater bronchial hyperresponsiveness and airway inflammation than did control mice.

“Our results support the hygiene hypothesis,” said lead author Hong Wei Chu, M.D. “Although mice are clearly different from humans, this kind of data, generated in a controlled experiment, adds important new evidence to help evaluate the hygiene hypothesis.”