Wu C Y, Sarfati M, Heusser C, Fournier S, Rubio-Trujillo M, Peleman R, Delespesse G
Research Center, Notre-Dame Hospital, University of Montreal, Quebec, Canada.
J Clin Invest. 1991 Mar;87(3):870-7. doi: 10.1172/JCI115092.
This study indicates that hydrocortisone (HC) markedly increases the synthesis of immunoglobulin E (IgE) by interleukin 4 (IL-4)-stimulated human lymphocytes. The effect is glucocorticoid specific and is obtained with low concentrations of HC (0.1-10 microM). In both the early and the late phase of the IL-4-induced response HC exerts its effects which are respectively IL-4 dependent and IL-4 independent. The IgE potentiation cannot be explained by the inhibition of interferon-gamma (IFN-gamma) production since it is observed in the absence of endogenous secretion of IFN-gamma. HC inhibits the production of IgE-binding factors (soluble CD23) and the expression of the low-affinity receptor for IgE, also known as the (Fc epsilon RII) CD23 antigen; however, the residual expression of Fc epsilon RII by IL-4- and HC-treated peripheral blood mononuclear cells (PBMCs) is important since the IgE response of these cells is markedly inhibited by anti-CD23 monoclonal antibody. HC acts mainly by amplifying the cellular interactions between monocytes and lymphocytes; indeed, HC has no effect on monocyte-depleted PBMCs, and moreover, monocytes cannot be replaced by soluble factors. Most importantly, T cells are not required for the induction of IgE synthesis by costimulation with IL-4 and HC. However, the IgE response of rigorously T cell-depleted PBMCs may be further increased by the addition of T cells. Further analysis of the permissive effect of HC on the synthesis of IgE by T cell-depleted PBMCs suggests that HC acts in synergy with IL-4 to trigger the activation and the differentiation of B cells into IgE-producing cells.
本研究表明，氢化可的松（HC）可显著增加白细胞介素4（IL-4）刺激的人淋巴细胞合成免疫球蛋白E（IgE）。该效应具有糖皮质激素特异性，且在低浓度HC（0.1 - 10微摩尔）时即可出现。在IL-4诱导反应的早期和晚期，HC均发挥作用，早期作用依赖于IL-4，晚期作用则不依赖于IL-4。IgE增强作用不能用抑制干扰素-γ（IFN-γ）产生来解释，因为在无内源性IFN-γ分泌的情况下也能观察到该现象。HC抑制IgE结合因子（可溶性CD23）的产生以及IgE低亲和力受体（也称为FcεRII CD23抗原）的表达；然而，经IL-4和HC处理的外周血单个核细胞（PBMC）中FcεRII的残留表达很重要，因为这些细胞的IgE反应会被抗CD23单克隆抗体显著抑制。HC主要通过增强单核细胞与淋巴细胞之间的细胞相互作用发挥作用；实际上，HC对单核细胞缺失的PBMC没有影响，而且单核细胞不能被可溶性因子替代。最重要的是，用IL-4和HC共刺激诱导IgE合成不需要T细胞。然而，严格去除T细胞的PBMC的IgE反应可通过添加T细胞进一步增强。对HC对去除T细胞的PBMC合成IgE的允许作用的进一步分析表明，HC与IL-4协同作用，触发B细胞活化并分化为产生IgE的细胞。
