credit: Amanda Rohde
For decades, the incidence of allergies and autoimmune diseases in the Western world has been a scientific puzzle. As rates of asthma, hay fever and lupus have skyrocketed in industrial nations, the number of cases in less developed countries remains relatively low.
Many scientists have attributed this disparity to a seemingly unlikely cause—citizens of first-world countries are becoming too clean.
This so-called "hygiene hypothesis" was born in 1989, when British epidemiologist David Strachan published a study in the British Medical Journal on chronic allergic illness among siblings. Strachan found that younger children with many older siblings were less likely to develop hay fever than their brothers and sisters, or children with few or no siblings. Strachan proposed that these younger siblings were protected from developing allergies because their older brothers and sisters constantly exposed them to new microbes. This exposure, he suggested, trained the younger children's immune systems to attack real pathogens, and made them less likely to mount allergic responses.
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Strachan's theory was subsequently expanded as a way to explain the Western world's rising rates of allergies and autoimmune diseases—those in which the immune system misguidedly attacks the body's own cells. The hygiene hypothesis posits that people who live in industrialized societies have immune systems that are not regularly challenged by microbes; therefore, they overreact to pollen and other relatively benign foreign invaders.
"If you're fighting off assault on your life constantly, you just don't have time to sweat the little stuff."
"The basic mechanistic hypothesis that many people favor now is that you need robust pathogen exposure early in life to develop a robust immune system for later in life," said Christopher Karp, an immunologist at the University of Cincinnati.
Though researchers have amassed circumstantial support for this hypothesis, direct experimental corroboration has been scant. Recently, researchers at Duke University bolstered the theory with physical evidence gathered from wild and laboratory rodents.
Wild rats are constantly exposed to environmental antigens—molecules that provoke an immune response—while laboratory-raised rodents are more sheltered. This difference in antigen exposure between rat populations parallels the exposure between humans in industrialized and non-industrialized countries, said William Parker, an immunologist at Duke University and lead researcher of a study that will be published in the August issue of the Scandinavian Journal of Immunology.
An animal's immune system is designed to fight off antigens. When an antigen—such as an allergen or parasite—enters the body, the immune system manufactures antibodies, which attack the antigens. Allergic reactions and autoimmune disorders are caused by over-reactions on the part of a class of antibodies known as immunoglobulins.
Parker's team found that wild rodents have much higher levels of certain antibodies—known as immunoglobulin E (IgE) and immunoglobulin G (IgG)—than their laboratory counterparts. In humans, Parker said, IgE is involved in allergic reactions, while IgG has been linked to autoimmune diseases.
When a lab rat begins to manufacture immunoglobulins, it typically means it's been exposed to an antigen and that it's sick. Yet, the wild rodents Parker studied were perfectly healthy, despite the kind of elevated IgE and IgG levels that would indicate illness in their lab-reared peers.
Parker postulates that these chronically high antibody levels may be key to the hygiene hypothesis.
Because wild rats have such consistently elevated antibody quantities, the level at which antigens will spur an immune system response is also high. The threshold is so great that Parker believes common allergens and autoimmune disease antigens won't even register in the immune systems of wild rodents.
"If you're fighting off assault on your life constantly—you're battling it out everyday trying to live, trying to survive—you just don't have time to sweat the little stuff," Parker said. "You just don't have time to worry about a pollen grain because there are other things that are trying to kill you."