Original Article
Enhanced IL-4 Production and IL-4 Receptor Expression in Atopic Dermatitis and Their Modulation by Interferon-Gamma

https://doi.org/10.1111/1523-1747.ep12616114Get rights and content
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The in vivo and in vitro immunomodulatory effects of interferon gamma (IFN-γ) treatment on peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis (AD) and elevated IgE levels were studied. As part of a double blind placebo-controlled clinical trial, 14 AD patients were treated with IFN-γ (n = 7) or saline (n = 7) for 12 weeks. To assess the in vivo effects of IFN-γ treatment on interleukin (IL)-4-dependent lymphocyte function, we assessed the proliferation of AD PBMC in response to IL-4. Prior to IFN-γ treatment, AD PBMC had proportionately decreased proliferative responses to IL-4 when compared to IL-2. After 12 weeks of in vivo treatment with IFN-γ, there was an increase of IL-4-but not IL-2-induced lymphocyte proliferation in seven of eight AD patients.

To further study the immunologic basis of these observations, we studied the expression of IL-4 receptor (IL-4R) mRNA and the production of IL-4 by PBMC from AD patients. PBMC from AD patients expressed higher levels of IL-4R mRNA and produced significantly higher amount of IL-4 than normal controls (p < 0.05). More importantly, the in Vitro addition of IFN-γ caused significant reduction in both IL-4R mRNA expression and IL-4 production of PBMC from AD and non-atopic controls.

These data indicate that AD is characterized by an in vivo overstimulation of the IL-4- IL-4R pathway. The poor proliferative responses of untreated AD PBMC to exogenous IL-4 may be due to increased levels of endogenous IL-4 production with constant occupancy of the IL-4R. Furthermore, in vivo and in vitro treatment with IFN-γ down-regulates this pathway.

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