IFN-beta inhibits the ability of T lymphocytes to induce TNF-alpha and IL-1beta production in monocytes upon direct cell-cell contact.
IFN-beta inhibits the ability of T lymphocytes to induce TNF-alpha and IL-1beta production in monocytes upon direct cell-cell contact.
复制标题
IFN-β 抑制 T 淋巴细胞在细胞与细胞直接接触时诱导单核细胞产生 TNF-α 和 IL-1β 的能力。
作者：
F. Jungo;J. Dayer;C. Modoux;N. Hyka;D. Burger
肿瘤坏死因子 (TNF)-α 和白细胞介素 (IL-)1β 是免疫炎症性疾病发病机制中的重要参与者，通过与受刺激的 T 淋巴细胞直接接触，在单核细胞中被强烈诱导。本研究表明后一种机制被干扰素（IFN）-β 抑制。在植物血凝素 (PHA) 刺激的自体 T 淋巴细胞和单核细胞的共培养物中，IFN-β 分别抑制 TNF-α 和 IL-1β 的产生 88% 和 98%，而同时产生的 IL-1 受体拮抗剂 (IL-1Ra) 则增强两倍。 IFN-β 的后者作用与 IFN-γ、IL-4 和 IL-10 产生的调节无关。当单核细胞被受刺激的 T 细胞质膜激活时，IFN-β 会轻微抑制 TNF-α 和 IL-1β 的产生，同时将 IL-1Ra 的产生增强 1.5 倍。后一种效应与激活 24 小时后 IL-1Ra mRNA 高稳态水平的持续存在相关。在存在 IFN-β 的情况下，从 T 淋巴细胞中分离出的膜诱导单核细胞产生 IL-1β 和 TNF-α 的能力下降了 80%，而 IL-1Ra 的诱导能力仅下降了 32%。这些结果表明，IFN-β通过作用于T淋巴细胞和单核细胞来调节接触介导的单核细胞活化，降低T淋巴细胞诱导单核细胞中TNF-α和IL-1β产生的能力，并直接增强后者细胞中IL-1Ra的产生。
Tumour necrosis factor (TNF)-alpha and interleukin (IL-)1beta, essential players in the pathogenesis of immuno-inflammatory diseases, are strongly induced in monocytes by direct contact with stimulated T lymphocytes. The present study shows that the latter mechanism is inhibited by interferon (IFN)-beta. In co-cultures of autologous T lymphocytes and monocytes stimulated by phytohaemagglutinin (PHA), IFN-beta inhibited the production of TNF-alpha and IL-1beta by 88 and 98%, respectively, whereas the simultaneous production of IL-1 receptor antagonist (IL-1Ra), was enhanced two-fold. The latter effects of IFN-beta were independent of modulations in IFN-gamma, IL-4 and IL-10 production. When monocytes were activated by plasma membranes of stimulated T cells, IFN-beta slightly inhibited the production of TNF-alpha and IL-1beta, while enhancing 1.5-fold that of IL-1Ra. The latter effect correlated with the persistence of high steady-state levels of IL-1Ra mRNA after 24 h of activation. Membranes isolated from T lymphocytes that had been stimulated in the presence of IFN-beta displayed a 80% decrease in their capacity to induce the production of IL-1beta and TNF-alpha in monocytes, whereas IL-1Ra induction was decreased by only 32%. These results demonstrate that IFN-beta modulates contact-mediated activation of monocytes by acting on both T lymphocytes and monocytes, decreasing the ability of T lymphocytes to induce TNF-alpha and IL-1beta production in monocytes and directly enhancing the production of IL-1Ra in the latter cells.