Marfaing-Koka A, Maravic M, Humbert M, Galanaud P, Emilie D
INSERM U131, Institut Paris-Sud sur les Cytokines, Clamart, France.
Int Immunol. 1996 Oct;8(10):1587-94. doi: 10.1093/intimm/8.10.1587.
RANTES is a chemokine produced in delayed-type hypersensitivity (DTH) and allergic reactions, in which it may contribute to the recruitment of immune cells. Macrophages participate in the cellular infiltration in both conditions and they represent a potent source of RANTES. To understand the regulation of RANTES production by human monocytes, we analyzed the effect of cytokines and of corticosteroids on this production. We showed that IFN-gamma and tumor necrosis factor (TNF)-alpha cooperated to induce RANTES production by monocytes. N-acetylcysteine inhibited this effect, indicating that reactive oxygen intermediates are required for RANTES production. Both IL-10 and corticosteroids antagonized the stimulating effect of IFN-gamma and TNF-alpha on RANTES production. In contrast, IL-4 had no effect on IFN-gamma-induced RANTES production and it potentiated the positive effect of TNF-alpha on this production. Thus, the deactivating properties of IL-10 and corticosteroids on macrophage functions include RANTES production, and this may contribute to the immunosuppressive effect of both compounds in DTH and allergic reactions. In contrast, IL-4 has an opposite effect on RANTES production and this property may contribute to cell recruitment in allergic reactions. Therefore, although IL-10 and IL-4 belong to the Th2 family of cytokines, they can display distinct functions in immune reactions.
调节激活正常T细胞表达和分泌的因子（RANTES）是一种在迟发型超敏反应（DTH）和过敏反应中产生的趋化因子，在这些反应中它可能有助于免疫细胞的募集。巨噬细胞在这两种情况下都参与细胞浸润，并且它们是RANTES的重要来源。为了了解人单核细胞对RANTES产生的调节作用，我们分析了细胞因子和皮质类固醇对这种产生的影响。我们发现，γ干扰素（IFN-γ）和肿瘤坏死因子（TNF）-α协同诱导单核细胞产生RANTES。N-乙酰半胱氨酸抑制了这种作用，表明活性氧中间体是RANTES产生所必需的。白细胞介素（IL）-10和皮质类固醇均拮抗IFN-γ和TNF-α对RANTES产生的刺激作用。相反，IL-4对IFN-γ诱导的RANTES产生没有影响，并且它增强了TNF-α对这种产生的正向作用。因此，IL-10和皮质类固醇对巨噬细胞功能的失活特性包括RANTES的产生，这可能有助于这两种化合物在DTH和过敏反应中的免疫抑制作用。相反，IL-4对RANTES产生具有相反的作用，并且这种特性可能有助于过敏反应中的细胞募集。因此，尽管IL-10和IL-4属于Th2细胞因子家族，但它们在免疫反应中可以表现出不同的功能。
