Prostaglandin E(2) control of T cell cytokine production is functionally related to the reduced lymphocyte proliferation in atopic dermatitis

Past studies of peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis (AD) have demonstrated reduced proliferation. We have studied phytohemagglutinin-induced lymphocyte proliferation in the context of interleukin-4 (IL-4), interferon-gamma (IFN-gamma), and prostaglandin E(2) (PGE(2)) production in cultures of PBMC from patients without and with AD. The production index was found to correlate proportionally to IFN-gamma production and inversely to T-cell IL-4 and monocyte PGE(2) production. Assays in parallel cultures showed significantly increased PGE(2) production by purified AD monocytes. The proliferation index in PBMC from persons with AD was significantly reduced compared with normal PBMC. This difference was normalized in the presence of extrinsic IFN-gamma but exaggerated when IL-4 was added. Increased AD monocyte production of inflammatory factors (e.g., PGE(2)) and cytokines appears to increase IL-4 production by Th2 while suppressing IFN-gamma by Tk1. Restoration of the normal proliferation of PBMC by the addition of IFN-gamma may represent one mechanism for the clinical efficacy of IFN-gamma treatment of AD.