DECREASED INTERFERON-GAMMA AND INCREASED INTERLEUKIN-4 PRODUCTION IN ATOPIC-DERMATITIS PROMOTES IGE SYNTHESIS
DECREASED INTERFERON-GAMMA AND INCREASED INTERLEUKIN-4 PRODUCTION IN ATOPIC-DERMATITIS PROMOTES IGE SYNTHESIS
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DOI：
10.1016/s0091-6749(05)80010-7
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发表时间：
1992-09-01
影响因子：
14.2
通讯作者：
LEUNG, DYM
中科院分区：
文献类型：
--
作者：
JUJO, K;RENZ, H;LEUNG, DYM
特应性皮炎（AD）中IgE合成增加的机制尚不清楚，但可能与干扰素γ（IFN-γ）减少和/或白细胞介素（IL）-4产生增加有关。在这项研究中，我们研究了21例AD患者，6例银屑病患者和22名非特应性健康对照者的外周血单个核细胞（PBMC）的IFN-γ和IL-4的产生与刀豆球蛋白A（Con A）刺激后。AD PBMC的Con A诱导的增殖反应与健康对照的反应相似（p = 0.9）。然而，在有丝分裂原刺激后，AD培养物上清液与来自非特异性对照的上清液相比含有显著更少的IFN-γ（p = 0.001）但增加IL-4（p = 0.001）。相比之下，银屑病患者的PBMC在体外产生正常水平的IFN-γ和IL-4。由于已知IL-4减少IFN-γ合成，我们检查了中和抗IL-4对IFN-γ产生的影响。抗IL-4显著增加AD患者（p = 0.008）和非特异性对照（p = 0.02）的IFN-γ产生，但未使AD PBMC的IFN-γ产生正常化。来自AD PBMC的上清液，而不是来自非特异性PBMC的上清液，诱导来自非特异性供体的PBMC中的IgE合成（p = 0.02）。当将阻断IFN-γ的细胞结合的抗IFN-γ受体抗体加入到来自非特异性对照的上清液中时，其诱导IgE合成的能力显著更大（p = 0.03）。这些结果表明IL-4和IFN-γ产生的不平衡，这可能有助于AD中IgE合成的增加。
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.