The Increased Prevalence of Allergy and the Hygiene Hypothesis: Missing Immune Deviation, Reduced Immune Suppression, or Both?

Allergic atopic disorders, such as rhinitis, asthma, and atopic dermatitis, are the result of a systemic inflammatory reaction triggered by type 2 T helper (Th2) cell-mediated immune responses against 'innocuous' antigens (allergens) of complex genetic and environmental origin. A number of epidemiological studies have suggested that the increase in the prevalence of allergic disorders that has occurred over the past few decades is attributable to a reduced microbial burden during childhood, as a consequence of Westernized lifestyle (the 'hygiene hypothesis'). However, the mechanisms by which the reduced exposure of children to pathogenic and nonpathogenic microbes results in enhanced responses of Th2 cells are still controversial. The initial interpretation proposed a missing immune deviation of allergen-specific responses from a Th2 to a type 1 Th (Th1) profile, as a result of the reduced production of interleukin-12 and interferons by natural immunity cells which are stimulated by bacterial products via their Toll-like receptors. More recently, the role of reduced activity of T regulatory cells has been emphasized. The epidemiological findings and the experimental evidence available so far suggest that both mechanisms may be involved. A better understanding of this question is important not only from a theoretical point of view, but also because of its therapeutic implications.