Blotta M H, DeKruyff R H, Umetsu D T
Department of Pediatrics, Stanford University, CA 94305, USA.
J Immunol. 1997 Jun 15;158(12):5589-95.
We examined the effects of corticosteroids on IL-12 production by human monocytes and on cytokine synthesis in T cells. To distinguish the effects of corticosteroids on the APC used to activate the T cell from direct effects of corticosteroids on the T cell, experiments were performed by exposing the APC and not the T cell to corticosteroids. We found that corticosteroids significantly inhibited the production in monocytes of IL-12, a cytokine that is extremely potent in enhancing IFN-gamma and inhibiting IL-4 synthesis in T cells. We demonstrated that reduced production of IL-12 in corticosteroid-treated monocytes resulted in a decreased capacity of the monocytes to induce IFN-gamma and an increased ability to induce IL-4 in T cells. These results suggest that although corticosteroids may be beneficial for the treatment of asthma or allergic disease due to direct inhibitory effects of corticosteroids on cytokine synthesis in T cells, chronic corticosteroid therapy may indirectly exacerbate the long-term course of allergic disease. This deleterious effect of corticosteroids would result from a limitation in IL-12 production in tissue monocytes and macrophages, which would enhance production of Th2 cytokines (which augment allergic disease), and would reduce production of Th1 cytokines (which attenuate allergic disease) in T cells that subsequently infiltrate the tissues.
我们研究了皮质类固醇对人单核细胞产生白细胞介素-12（IL-12）以及对T细胞中细胞因子合成的影响。为了区分皮质类固醇对用于激活T细胞的抗原呈递细胞（APC）的作用与皮质类固醇对T细胞的直接作用，我们通过将APC而非T细胞暴露于皮质类固醇来进行实验。我们发现，皮质类固醇显著抑制单核细胞中IL-12的产生，IL-12是一种在增强T细胞中γ干扰素（IFN-γ）产生及抑制白细胞介素-4（IL-4）合成方面极具效力的细胞因子。我们证明，经皮质类固醇处理的单核细胞中IL-12产生的减少导致单核细胞诱导IFN-γ的能力下降，而诱导T细胞中IL-4的能力增强。这些结果表明，尽管皮质类固醇可能因其对T细胞中细胞因子合成的直接抑制作用而对哮喘或过敏性疾病的治疗有益，但长期使用皮质类固醇治疗可能会间接加剧过敏性疾病的长期病程。皮质类固醇的这种有害作用将源于组织中的单核细胞和巨噬细胞产生IL-12的能力受限，这会增强Th2细胞因子（加剧过敏性疾病）的产生，并减少随后浸润组织的T细胞中Th1细胞因子（减轻过敏性疾病）的产生。
