Enhanced prostaglandin E2 production by monocytes in atopic dermatitis (AD) is not accompanied by enhanced production of IL-6, IL-10 or IL-12

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Abstract
AD is associated with a bias of the T helper cells to show increased IL-4 and reduced interferon-gamma (IFN-γ) production. The production of IFN-γ and IL-4 and the development of Th cells into either high IFN-γ or high IL-4 producers is strongly influenced by factors produced by antigen-presenting cells (APC), like IL-12 and prostaglandin E2 (PGE2). IL-12 selectively enhances IFN-γ production and favours the development of IFN-γ-producing Th cells, whereas PGE2 selectively inhibits IFN-γ production by Th cells. The aim of this study was to test whether the increased IL-4/IFN-γ production ratio by Th cells in AD can be explained by an increased PGE2/IL-12 production ratio by the APC. Monocytes were used as APC source. PGE2 and IL-12 production by lipopolysaccharide (LPS)-stimulated monocytes from 12 AD patients and 12 non-atopic controls was determined using two complementary experimental systems, whole blood cultures and purified monocytes. In addition, we determined IL-6 production as a measure of monocyte activation, and IL-10 production because IL-12 production by monocytes is highly influenced by endogenously produced IL-10. The monocytes from AD patients showed normal production levels of IL-6 and IL-10, a two-fold, but non-significant decrease in IL-12 production, and a significantly (three-fold) higher PGE2 production than those from non-atopic controls. Here we show for the first time that enhanced PGE2 production by monocytes in AD is not accompanied by a general rise in cytokine production. We conclude that AD is indeed associated with an increased PGE2/IL-12 production ratio by monocytes.