Development of the Capacity of Peripheral Blood Mononuclear Cells to Produce IL-4, IL-5 and IFN-γ upon Stimulation with House Dust Mite in Children with Atopic Dermatitis

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Abstract
Background: Imbalances of IL-4 and IFN-γ production are widely known to increase IgE synthesis in allergic individuals, and IL-5 is known to play a critical role in the pathogenesis of various allergic diseases. However, little is known about how Th cells specific to house dust mite (HDM) develop the capacity to produce these cytokines in children with atopic dermatitis (AD). Objective: This study aims to clarify when HDM-specific Th cells develop the capacity to produce IL-4, IL-5 and IFN-γ in children with AD. Methods: The production of IL-4, IL-5 and IFN-γ by peripheral blood mononuclear cells (PBMCs) upon stimulation with HDM was measured in 91 children with AD and 37 control subjects. The changes in the cytokine production with age were analyzed transectionally and longitudinally. Results: IL-4 production by HDM-stimulated PBMCs in children with AD was already increased before age 1. Thereafter, it continuously rose until reaching a near-maximum level at age 2. Growth-related changes in the production of IL-5 resembled those in the production of IL-4 and peaked at age 1. The production of these cytokines was very low in control subjects up to age 2 and then gradually increased, albeit never above the levels measured in AD children. The production of IFN-γ in children with AD reached a near-maximum level during the first year of life and diminished after age 3. Although IFN-γ production in controls was lower than that in AD children during infancy, it continuously rose even after age 3 and surpassed the levels measured in AD children. The level of serum HDM-specific IgE antibody began to increase after age 1 following the rise of IL-4 production. Essentially the same relationship among IL-4, IFN-γ and IgE synthesis was seen in a longitudinal study of 6 AD infants, in whom HDM-specific IgE was initially negative but later turned positive. Conclusions: These findings suggest that the capacity of HDM-specific Th cells to produce IL-4, IL-5 and IFN-γ develops and effectively matures during the first 3 years of life in children with AD.