The hygiene hypothesis and atopy: bring back the parasites?

A topy has been increasing in prevalence in the industrialized world for at least two decades, but the same increase has not been noted in the developing world. The hygiene hypothesis suggests that lack of exposure to infectious agents during childhood results in a balance of T helper 1 (Th1) and T helper 2 (Th2) type immune responses that favor atopy. Typical Th1 cytokines include IL-12 and interferon (IFN)-g, whereas Th2 cytokines include IL-4, IL-5, IL-9, and IL-13. Most antimicrobial responses are Th1 responses, whereas atopy is associated with a Th2 pattern of cytokines. The hygiene hypothesis has gained significant credibility, but is not universally accepted. It should be noted that most of the evidence in favor of the hypothesis is in the form of population-based studies of incidence and association, but there is currently no proof of causation. Studies have varied in their methods, with some relying on historic data, and some using skin test positivity rather than clinical disease manifestations as a measured outcome. There are prospective data supporting an inverse relationship between atopic dermatitis and endotoxin exposure, early day care, and animal exposure, but other data suggest a positive association between infections in early life and atopic dermatitis. Infections that have been negatively associated with atopy include geohelminths in warmer climates and hepatitis A, Helicobacter pylori, and toxoplasma in temperate climates. Mycobacteria have been hypothesized to play a role in a range of climates.