The modulation of cytokine and IgE production by tumor necrosis factor-beta in atopic dermatitis

Atopic dermatitis (AD) is associated with increased IL-4, IL-5, and IL-13 b ut decreased IFN-gamma production. This cytokine profile may account for th e atopic features of this illness, including IgE upregulation. Recent studi es have demonstrated that tumor necrosis factor (TNF)-beta is produced by T h1-like cells, but the cytokine modulation by TNF-beta and the clinical sig nificance of this cytokine in AD is not known. Therefore, this study was ca rried out to determine the potential role of TNF-beta in AD. In this study, we cultured peripheral blood mononuclear cells from patients with AD and n ormal subjects with anti-CD3 monoclonal antibodies and investigated the pro duction of TNF-beta by ELISA. The mean +/- SEM of TNF-beta production in AD was significantly lower than normal subjects (p = 0.03). The effect of TNF -beta on cytokine production was investigated by culturing peripheral blood mononuclear cells with anti-CD3 monoclonal antibodies in the presence or a bsence of TNF-beta. Compared with medium control, TNF-beta significantly de creased IL-5 (p = 0.0004) and IL-13 (p = 0.008) but increased IFN-gamma (p = 0.001) production. The effect of TNF-beta on IgE production was determine d by culturing peripheral blood mononuclear cells in the IL-4- and anti-CD4 0-induced IgE production system. Interestingly, TNF-beta significantly decr eased IgE (p = 0.02), but not IgG production compared with medium control. Our study demonstrates that TNF-beta production is downregulated in AD. Thi s cytokine increases IFN-gamma production but decreases IL-5, IL-13, as wel l as IgE production. These findings suggest a potential role for TNF-beta i n the pathogenesis of AD.