Selective development of a strong Th2 cytokine profile in high-risk children who develop atopy: risk factors and regulatory role of IFN-gamma, IL-4 and IL-10

Background The immunological processes in early life and their relation to allergic sensitization leading to a Th2 cytokine profile are still not well understood. Objective To analyse the environmental and genetic risk factors and immunol ogical responses at birth in relation to the development of atopic disease at 12 months of age in a longitudinal study of high-risk children. Methods High-risk children were followed from birth till 12 months of age. Mononuclear cells obtained at birth and 6 and 12 months thereafter were ana lysed for their proliferative and cytokine responses after polyclonal and a llergen-specific stimulation. Results At 12 months of age 25% children had developed an atopic disease. T wo atopic parents, parental smoking and atopic dermatitis of at least one o f the parents were significant risk factors. In cord blood of newborns who developed atopy, an increased percentage of CD4(+)CD45RO(+) cells and an in creased polyclonal-stimulated proliferation were observed. Furthermore, an impaired allergen-induced, but not polyclonal-stimulated IFN-gamma producti on was found, suggesting a regulatory defect. At 6 and 12 months of age, a strong Th2 profile (characterized by increased levels of IL-4, IL-5, and IL -13) after both polyclonal and, to a lesser extent, allergen-specific stimu lation was found in the children developing atopy. Allergen-induced IL-10 p roduction at 12 months of age was only observed in the non-atopic children. Conclusion Our data indicate that the first 6 months of life represent a cr itical time window for the initiation of immunological changes resulting in the development of atopy. The selective development of a Th2 cytokine prof ile in high-risk children who develop atopy is due to increased production of Th2 cytokines, possibly caused by impaired allergen-induced IFN-gamma pr oduction in the neonatal period. Further-more, the decreased allergen-induc ed IL-10 levels observed in the atopic children at 12 months of age may res ult in a lack of down-regulation of the inflammatory process.