Der Bauernhofeffekt als Modellsitutation zur Hygienehypothese - Einblicke in pränatale immunologische Regulationsmechanismen

Allergic disorders have become a major public health problem in industrialized countries. There has been a continuous increase in their prevalence and incidence. At present more than 20% of the European population suffers from allergic diseases. The aetiology of allergic diseases remains poorly understood despite considerable research. In 1989, the concept of the Hygiene Hypothesis was proposed by Strachan et al.. It states that high living standards and hygienic conditions are correlated with an increased risk for the development of allergic diseases. In further studies, it could be shown that children growing up on a farm had a lower prevalence of IgE-mediated allergic diseases than their peers living in urban regions. Epidemiologic studies now indicate that this “farm effect” arises not only from postnatal but even prenatal farm exposures. Therefore it is supposable that the immune status of a newborn, born in close proximity to farm, already differs. AIM: As part of the PASTURE-Project, the thesis is aimed to assess the effect of maternal traditional farm life exposure on the foetal immune status, particularly with regard to the markers of ‘TH1/TH2-lymphocytes’. METHODES: IL-5 (reflecting TH2-immunity), IL-10 (reflecting Treg cells), IFN-γ (reflecting TH1-immunity), IL-12 and TNF-α (reflecting innate immunity) were measured quantitatively in cord blood samples of farm and non farm exposed newborns after stimulation with PMA/Ionomycin. This panel provides important insight into the overall status of T-cell effector function in the newborns. To investigate which particular environmental exposure has an effect on these cytokines, the results of the PASTURE population were associated with demographic factors and typical farm exposures. Furthermore, these associations were compared to an Austrian subpopulation to reveal country-specific differences with regard to exposures and cytokine expression within the population of the PASTURE-study. RESULTS: Our results show that prenatal farm exposure affects the cytokine production of cord blood mononuclear cells. Significant positive associations could be found particularly between the proinflammatory cytokines IFN-γ ( TH1-cells: adaptive immune system) and TNF-α ( innate immune system) and the farm status. The associations concerning IFN-γ could be linked mainly to maternal contact to farm animals during pregnancy. Differences between the Austrian subpopulation and the whole PASTURE-population concerning cytokine expression became apparent, supposable due to variability of the engaged exposures, containing country specific differences of agricultural practices. No significant associations could be found in proinflammatory cytokines within the Austrian results. Our data shows an increasing effect of maternal exposure to hayricks during pregnancy in Austrian neonates for IL-10. CONCLUSION: The combination of epidemiological and immunological results in this thesis provides new insights into priming and maturation of the foetal immune system. The traditional farm environment influences the developing immune system already prenatally towards a TH1-dominated immune profile, particularly when the mother has had contact with farm animals during pregnancy. The association between the early TH1-response and the development of allergic diseases later on will be shown in the course of PASTURE-Study. In this way the relationship between the shifted immune response and a potentially associated protection against allergies will also be elucidated.