Renz H, Jujo K, Bradley K L, Domenico J, Gelfand E W, Leung D Y
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
J Invest Dermatol. 1992 Oct;99(4):403-8. doi: 10.1111/1523-1747.ep12616114.
The in vivo and in vitro immunomodulatory effects of interferon gamma (IFN-gamma) 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-gamma (n = 7) or saline (n = 7) for 12 weeks. To assess the in vivo effects of IFN-gamma treatment on interleukin (IL)-4-dependent lymphocyte function, we assessed the proliferation of AD PBMC in response to IL-4. Prior to IFN-gamma 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-gamma, 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 amounts of IL-4 than normal controls (p less than 0.05). More importantly, the in vitro addition of IFN-gamma caused significant reduction in both IL-4R and 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 on the IL-4R. Furthermore, in vivo and in vitro treatment with IFN-gamma down-regulates this pathway.
研究了干扰素γ（IFN-γ）治疗对特应性皮炎（AD）患者且IgE水平升高的外周血单个核细胞（PBMC）的体内和体外免疫调节作用。作为双盲安慰剂对照临床试验的一部分，14例AD患者接受IFN-γ（n = 7）或生理盐水（n = 7）治疗12周。为了评估IFN-γ治疗对白细胞介素（IL）-4依赖性淋巴细胞功能的体内影响，我们评估了AD患者PBMC对IL-4的增殖反应。在IFN-γ治疗前，与IL-2相比，AD患者PBMC对IL-4的增殖反应成比例降低。在接受IFN-γ体内治疗12周后，8例AD患者中有7例IL-4诱导的淋巴细胞增殖增加，但IL-2诱导的未增加。为了进一步研究这些观察结果的免疫学基础，我们研究了AD患者PBMC中IL-4受体（IL-4R）mRNA的表达和IL-4的产生。AD患者的PBMC表达的IL-4R mRNA水平更高，产生的IL-4量也明显高于正常对照（p < 0.05）。更重要的是，体外添加IFN-γ可使AD患者和非特应性对照的PBMC中IL-4R和mRNA表达以及IL-4产生显著降低。这些数据表明，AD的特征是IL-4-IL-4R途径在体内过度刺激。未经治疗的AD患者PBMC对外源性IL-4的增殖反应较差可能是由于内源性IL-4产生水平增加且IL-4R持续被占据。此外，IFN-γ的体内和体外治疗可下调该途径。
