EFFECTS OF IFN-GAMMA AND IL-4 ON IL-1 PRODUCTION BY HUMAN MONOCYTES

在这个项目中，我们研究了两种不同的T细胞来源的影响 淋巴因子干扰素-γ和白介素4对人单核细胞功能的影响 产生IL-1。IL-4抑制高纯度正常人产生IL-1 单核细胞。我们发现，抑制是最大的或接近最大的 IL-4浓度低至ng/ml，当加入IL-4时最明显 在IL-1诱导之前或同时进行单核细胞培养 刺激措施，如脂多糖。Northern印迹分析表明，IL-4不仅 显著降低了IL-1β的稳态消息水平，但 同时检测肿瘤坏死因子α和白介素6。抑制作用不明显。 刺激特异性，因为IL-4抑制了三者诱导的IL-1的产生 不同的单核细胞激活刺激因子：脂多糖、PMA和金黄色葡萄球菌 考恩(Cowan)。此外，单核细胞表达相对较少的 高亲和力IL-4受体(L50-300R/细胞；KD-32药丸)提示 产生抑制作用所需的受体相对较少， 效果。尽管干扰素-γ和IL-4均上调MHC-II类抗原 单核细胞表达(HL A-DR)，对IL-1的作用相反 产生：干扰素-γ显著增加IL-1的产生 而IL-4则抑制IL-1的产生。 此外，IL-4在很大程度上中和了干扰素-γ的增强作用 提示IL-4可能是某些干扰素-γ的有效拮抗剂。 诱因效应。这些发现表明， 干扰素-γ和IL-4可能深刻影响IL-1、α 在控制单核/巨噬细胞方面可能很重要的特性 在特定组织部位的激活。这些发现还表明，IL-4 可能在治疗中作为抗炎药有临床应用价值 如类风湿性关节炎等疾病的过度表达 已观察到单因子IL-1、TNF-α和IL-6。

In this project we investigated the effects of two distinct T cell-derived lymphokines, IFN-gamma and IL-4, on the ability of human monocytes to produce IL-1. IL-4 inhibits IL-1 production by highly purified normal human monocytes. We have found that Inhibition Is maximal or near maximal with IL-4 concentrations as low as ng/ml and most pronounced when IL-4 is added to monocyte cultures prior to or simultaneous with an IL-1 inducing stimulus such as LPS. Northern blot analyses revealed that IL-4 not only dramatically, reduced the steady-state message levels for IL-1 beta but also those of TNF alpha and IL-6. The inhibitory effect was not stimulus-specific because IL-4 suppressed IL-1 production Induced by three distinct monocyte activation stimuli: LPS, PMA and Staphylococcus aureus Cowan (SAC). Furthermore, monocytes expressed a relatively small number of high affinity IL-4 receptors (l50-300R per cell; Kd - 32 pill) indicating that relatively few receptors are necessary to generate the inhibitory, effect. Although both IFN-gamma and IL-4 upregulated MHC class II antigen (HLA-DR) expression by monocytes, they exhibited opposite effects on IL-1 production: IFN-gamma significantly enhanced IL-1 production induced by submaximal concentrations of LPS; whereas, IL-4 suppressed IL-1 production. Moreover, IL-4 largely neutralized the potentiating effect of IFN-gamma suggesting that IL-4 may be an effective antagonist of certain IFN-gamma-- inducible effects. These findings demonstrate that the relative levels of IFN-gamma and IL-4 may profoundly influence the expression of IL-1, a property that may be important in the control of monocyte/macrophage activation at specific tissue sites. These findings also suggest that IL-4 might have clinical utility as an antiinflammatory agent in the treatment of diseases such as rheumatoid arthritis where overexpression of the monokines IL-1, TNF alpha and IL-6 has been observed.