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 but decreased IFN-gamma production. This cytokine profile may account for the atopic features of this illness, including IgE upregulation. Recent studies have demonstrated that tumor necrosis factor (TNF)-beta is produced by Th1-like cells, but the cytokine modulation by TNF-beta and the clinical significance of this cytokine in AD is not known. Therefore, this study was carried 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 normal subjects with anti-CD3 monoclonal antibodies and investigated the production 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 absence of TNF-beta. Compared with medium control, TNF-beta significantly decreased 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 determined by culturing peripheral blood mononuclear cells in the IL-4- and anti-CD40-induced IgE production system. Interestingly, TNF-beta significantly decreased IgE (p = 0.02), but not IgG production compared with medium control. Our study demonstrates that TNF-beta production is downregulated in AD. This cytokine increases IFN-gamma production but decreases IL-5, IL-13, as well as IgE production. These findings suggest a potential role for TNF-beta in the pathogenesis of AD.
Jirapongsananuruk
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O
Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Donahue
H L
HL
Trumble
A E
AE
Leung
D Y
DY
D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003876:Dermatitis, Atopic / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008233:Lymphotoxin-alpha / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D012016:Reference Values; D015854:Up-Regulation
D016207:Cytokines; D018793:Interleukin-13; D015848:Interleukin-5; D008233:Lymphotoxin-alpha; D007073:Immunoglobulin E; D007371:Interferon-gamma