Epidemiological and immunological evidence for the hygiene hypothesis.

Allergic diseases are inflammatory disorders that develop on the basis of complex gene-environment interactions. The prevalence of allergies is steadily increasing and seems to be associated with modern lifestyle. Therefore, it was hypothesized that high living standards and hygienic conditions are correlated with an increased risk for the development of an allergic disease. This so-called "hygiene hypothesis" states that due to reduced exposure to microbial components, the proposed allergy-preventing potential of these factors is no more present in sufficient qualities and/or quantities, which leads to an imbalance of the immune system with a predisposition to the development of allergic disorders. Meanwhile, several epidemiological studies were conducted supporting this concept and generating novel ideas for the underlying mechanisms that were then followed up by use of well-defined animal models and human studies. The current view of cellular and molecular mechanisms responsible for these phenomena includes changes in the fine balancing of T helper cell 1 (Th1), Th2 and regulatory T cell (Treg) responses which are triggered by altered or missing innate immune cell activation. In fact, proper activation of cells of the innate immune system via their so-called pattern recognition receptors has been demonstrated to play a crucial role in early shaping of the immune system and suppression of the development of Th2-driven allergic immune responses. These processes start already in utero and prenatal as well as early postnatal developmental stages seem to represent a certain "window of opportunity" for allergy-preventing environmental influences.