Foey A D, Feldmann M, Brennan F M
Kennedy Institute of Rheumatology, 1 Aspenlea Road, Hammersmith, London, W6 8LH, UK.
Cytokine. 2000 Oct;12(10):1496-505. doi: 10.1006/cyto.2000.0750.
Interleukin 10 is a potent anti-inflammatory and immunomodulatory cytokine. Little is known regarding its induction in monocytes/macrophages, however LPS, a reproducible trigger of IL-10, is augmented by direct contact with T cells. In this context, the role of CD40-ligation is investigated. In the rheumatoid synovium, IL-10 is produced by tissue macrophages. Monocytes primed with M-CSF, a cytokine present in rheumatoid joints, produced IL-1beta, TNF-alpha and IL-10 upon CD40-ligation at an IL-1: TNF-alpha: IL-10 ratio of 10:0.5:1. IFN-gamma-primed monocytes, however, predominantly produced TNF-alpha and IL-1beta. Both differentiated monocytes display an endogenous IL-10 activity regulatable by CD40 stimulation. Additionally, these monocytes display differential control by exogenous and endogenous IL-1 and TNF-alpha. M-CSF-primed monocyte IL-10 production was dependent on endogenous TNF-alpha and, to a lesser extent, IL-1, whereas IFN-gamma-primed monocytes were partially dependent on endogenous IL-1. The addition of exogenous IL-1 augments CD40 induced IL-10 production by IFN-gamma-primed monocytes. These data indicate that CD40 ligation regulates cell contact mediated macrophage IL-10 and that the route of differentiation determines the cytokine profile.
白细胞介素10是一种强效的抗炎和免疫调节细胞因子。然而，关于其在单核细胞/巨噬细胞中的诱导机制知之甚少，不过脂多糖（LPS）是白细胞介素10的一种可重复性触发因子，与T细胞直接接触可增强其作用。在此背景下，对CD40连接的作用进行了研究。在类风湿性滑膜组织中，白细胞介素10由组织巨噬细胞产生。用巨噬细胞集落刺激因子（M-CSF，类风湿性关节中存在的一种细胞因子）预处理的单核细胞，在CD40连接后会产生白细胞介素1β、肿瘤坏死因子-α和白细胞介素10，其比例为白细胞介素1:肿瘤坏死因子-α:白细胞介素10 = 10:0.5:1。然而，用γ干扰素预处理的单核细胞则主要产生肿瘤坏死因子-α和白细胞介素1β。这两种分化的单核细胞均表现出可通过CD40刺激调节的内源性白细胞介素10活性。此外，这些单核细胞对外源性和内源性白细胞介素1及肿瘤坏死因子-α表现出不同的调控作用。M-CSF预处理的单核细胞产生白细胞介素10依赖于内源性肿瘤坏死因子-α，在较小程度上还依赖于白细胞介素1，而γ干扰素预处理的单核细胞则部分依赖于内源性白细胞介素1。添加外源性白细胞介素1可增强γ干扰素预处理的单核细胞中CD40诱导的白细胞介素10的产生。这些数据表明，CD40连接调节细胞接触介导的巨噬细胞白细胞介素10的产生，并且分化途径决定了细胞因子谱。
