Bailly S, Ferrua B, Fay M, Gougerot-Pocidalo M A
INSERM U.294, Paris, France.
Cytokine. 1990 May;2(3):205-10. doi: 10.1016/1043-4666(90)90017-n.
Interleukin 6 (IL 6), IL 1 alpha, IL beta and tumor necrosis factor (TNF) alpha are four cytokines induced in monocytes by lipopolysaccharide (LPS); however, it is unclear whether the mechanisms which control their production are similar. In this study, we report the effects of prostaglandin E2 (PGE2), and two other cAMP-elevating agents, dibutyryl cAMP and 3-isobutyl-1-methyl-xanthine, on the in vitro LPS-induced production of IL 6, IL 1 alpha, IL 1 beta and TNF alpha by human monocytes. The production of these four cytokines was found to be selectively regulated in monocytes, by increases in intracellular cAMP levels. In effect, such agents enhanced, in a dose-dependent manner, both extracellular and cell-associated IL 6 production by LPS-stimulated monocytes. In contrast, it was confirmed, using the same samples, that these cAMP-elevating agents inhibit both extracellular and cell-associated TNF alpha production in a dose-dependent manner. IL 1 alpha and IL 1 beta production, measured by means of specific immunoreactive assays, were not significantly modified. Kinetic analysis showed that the potentiating effect of cAMP on IL 6 production, along with its inhibiting effect on TNF alpha production, could be seen as early as 1 hr after LPS stimulation. These results demonstrate that IL 6, TNF alpha, IL 1 alpha and IL 1 beta production can be differently modulated by an agent, PGE2, which is produced simultaneously by LPS-stimulated monocytes. Such differential autocrine modulation may play an important role in the regulation of the production of cytokines participating in immune and inflammatory responses.
白细胞介素6（IL - 6）、IL - 1α、IL - 1β和肿瘤坏死因子（TNF）α是四种由脂多糖（LPS）诱导单核细胞产生的细胞因子；然而，控制它们产生的机制是否相似尚不清楚。在本研究中，我们报告了前列腺素E2（PGE2）以及另外两种升高cAMP的试剂，二丁酰cAMP和3 - 异丁基 - 1 - 甲基黄嘌呤，对人单核细胞体外LPS诱导产生IL - 6、IL - 1α、IL - 1β和TNFα的影响。发现这四种细胞因子的产生在单核细胞中受到细胞内cAMP水平升高的选择性调节。实际上，这些试剂以剂量依赖性方式增强了LPS刺激的单核细胞的细胞外和细胞相关IL - 6的产生。相反，使用相同样本证实，这些升高cAMP的试剂以剂量依赖性方式抑制细胞外和细胞相关TNFα的产生。通过特异性免疫反应测定法测量的IL - 1α和IL - 1β的产生没有明显改变。动力学分析表明，cAMP对IL - 6产生的增强作用及其对TNFα产生的抑制作用早在LPS刺激后1小时就可以观察到。这些结果表明，LPS刺激的单核细胞同时产生的一种试剂PGE2可以对IL - 6、TNFα、IL - 1α和IL - 1β的产生进行不同的调节。这种差异自分泌调节可能在参与免疫和炎症反应的细胞因子产生的调节中起重要作用。
