Decreased interferon gamma and increased interleukin-4 production in atopic dermatitis promotes IgE synthesis

Abstract

The mechanism(s) responsible for increased IgE synthesis in atopic dermatitis (AD) are unknown, but they may be related to either decreased interferon gamma (IFN-gamma) and/or increased interleukin (IL)-4 production. In this study we examined peripheral blood mononuclear cells (PBMCs) from 21 patients with AD, six patients with psoriasis, and 22 nonatopic healthy controls for IFN-gamma and IL-4 production after stimulation with concanavalin A (Con A). The Con A-induced proliferative response of AD PBMCs was similar to the response of healthy controls (p = 0.9). After mitogen stimulation, however, AD culture supernatants contained significantly less IFN-gamma (p = 0.001) but increased IL-4 (p = 0.001) compared with supernatants from nonatopic controls. In contrast, PBMCs from patients with psoriasis produced normal levels of IFN-gamma and IL-4 in vitro. Since IL-4 is known to decrease IFN-gamma synthesis, we examined the effect of neutralizing anti-IL-4 on IFN-gamma production. Anti-IL-4 significantly increased IFN-gamma production in patients with AD (p = 0.008) and nonatopic controls (p = 0.02) but did not normalize IFN-gamma production by AD PBMCs. Supernatants from AD PBMCs, but not supernatants from nonatopic PBMCs, induced IgE synthesis in PBMCs from nonatopic donors (p = 0.02). When an anti-IFN-gamma receptor antibody, which blocks cellular binding of IFN-gamma, was added to supernatants from nonatopic controls their capacity to induce IgE synthesis was significantly greater (p = 0.03). These results demonstrate an imbalance of IL-4 and IFN-gamma production, which may contribute to increased IgE synthesis in AD.