Interleukin 1 induces interleukin 1. I. Induction of circulating interleukin 1 in rabbits in vivo and in human mononuclear cells in vitro.
Interleukin 1 induces interleukin 1. I. Induction of circulating interleukin 1 in rabbits in vivo and in human mononuclear cells in vitro.
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DOI：
10.4049/jimmunol.139.6.1902
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发表时间：
1987-09
影响因子：
4.4
通讯作者：
C. Dinarello;T. Ikejima;S. Warner;S. Orencole;G. Lonnemann;Joseph G. Cannon;P. Libby
中科院分区：
文献类型：
--
作者：
C. Dinarello;T. Ikejima;S. Warner;S. Orencole;G. Lonnemann;Joseph G. Cannon;P. Libby
白细胞介素1（IL-1）通过升高体温、诱导多种淋巴因子和肝急性期蛋白的合成以及作为淋巴细胞的化学引诱物在宿主防御机制中起重要作用。然而，在一些微环境中，如损伤组织或关节间隙，升高的IL-1水平可能导致病理过程，例如参与血管翳形成的组织的增殖和纤维化以及基质和异常组织结构的降解。为了研究可能导致IL-1过量产生的潜在机制，我们检测了IL-1通过诱导其自身基因表达导致生物活性IL-1合成而参与扩增事件的能力。当注射到兔子体内时，重组人IL-1-α诱导双相发热，并且在3小时后的第二次体温升高期间，通过将血浆被动转移到其他兔子体内检测到循环致热物质。双相热的诱导不是由重组IL-1的内毒素污染引起的。3小时循环热原是热不稳定的，并且不是残留注射的IL-1-α。经色谱分离和生物学测定，证实为新的兔源性IL-1。我们接下来将人血液单核细胞与重组IL-1-α孵育，并使用D10.G4.1鼠T细胞系通过生物测定测量IL-1的细胞内和细胞外水平。为了控制用于刺激单核细胞（MNC）的重组IL-1-α的携带，我们使用了对IL-1-α或IL-1-β具有特异性的中和抗体。这些中和的结果表明，重组人IL-1-α在体外诱导人MNC中IL-1-β的合成。这些结果用IL-1-β特异性放射免疫测定法进行了验证。在浓度为100 ng/ml时，IL-1-α诱导MNC培养物中前列腺素E2的产生，这与免疫反应性IL-1-β的产生减少有关。向培养物中加入吲哚美辛可以防止高浓度IL-1-α诱导的IL-1-β产生减少。使用非粘附MNC，我们观察到IL-1-β和IL-1-α mRNA在暴露于重组IL-1-α 4小时后增加。这些结果表明，IL-1-α在体外从MNC诱导生物活性和免疫活性IL-1-β，并且相同浓度的IL-1-α诱导两种形式IL-1的基因表达。（400字处截断摘要）
Interleukin 1 (IL-1) plays an important role in host defense mechanisms by increasing body temperature, inducing the synthesis of a variety of lymphokines and hepatic acute phase proteins and acting as a chemoattractant for lymphocytes. However, in some microenvironments such as injured tissue or joint spaces, elevated IL-1 levels may contribute to pathologic processes, for example, proliferation and fibrosis of tissue involved in pannus formation as well as degradation of matrix and abnormal tissue architecture. To investigate potential mechanisms that may lead to excessive production of IL-1, we have examined the ability of IL-1 to participate in an amplification event by inducing its own gene expression leading to synthesis of biologically active IL-1. When injected into rabbits, recombinant human IL-1-alpha induced biphasic fevers, and during the second temperature elevation 3 hr later, a circulating pyrogenic material was detected by passive transfer of plasma to other rabbits. Induction of the biphasic fever was not caused by endotoxin contamination of the recombinant IL-1. The 3-hr circulating pyrogen was heat-labile and was not residual injected IL-1-alpha. Chromatographic separation of this plasma and biologic assay suggested that it was new IL-1 of rabbit origin. We next incubated human blood mononuclear cells with recombinant IL-1-alpha and measured the intracellular and extracellular levels of IL-1 by bioassay using the D10.G4.1 murine T cell line. In order to control for the carryover of recombinant IL-1-alpha used to stimulate the mononuclear cells (MNC), we used neutralizing antibodies that were specific for IL-1-alpha or IL-1-beta. The results of these neutralizations showed that recombinant human IL-1-alpha induces the synthesis of IL-1-beta in human MNC in vitro. These results were verified with a radioimmunoassay specific for IL-1-beta. At concentrations of 100 ng/ml, IL-1-alpha induced prostaglandin E2 production in the MNC culture, and this was associated with decreased production of immunoreactive IL-1-beta. Adding indomethacin to the cultures prevented the decreased production of IL-1-beta induced by high concentrations of IL-1-alpha. Using nonadherent MNC, we observed an increase in IL-1-beta as well as IL-1-alpha mRNA after 4 hr of exposure to recombinant IL-1-alpha. These results demonstrate that IL-1-alpha induces biologically active and immunoreactive IL-1-beta from MNC in vitro and that the same concentrations of IL-1-alpha induce gene expression for both forms of IL-1.(ABSTRACT TRUNCATED AT 400 WORDS)