Biological activity and brain actions of recombinant rat interleukin-1alpha and interleukin-1beta.
Biological activity and brain actions of recombinant rat interleukin-1alpha and interleukin-1beta.
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重组大鼠白介素-1α和白细胞介素-1β的生物活性和脑作用。
DOI：
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发表时间：
1998
影响因子：
2.8
通讯作者：
Emmanuelle Wollman
中科院分区：
文献类型：
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作者：
H. R. Anforth;R. Bluthé;Adrian Bristow;S. J. Hopkins;M. Lenczowski;G. Luheshi;J. Lundkvist;B. Michaud;Y. Mistry;A.;Chai Zhen;Robert Dantzer;Stephen Poole;N. J. Rothwell;F. J. Tilders;Emmanuelle Wollman;Emmanuelle Wollman
IL-1 α和IL-1 β对中枢神经系统具有强效作用，导致发热、下丘脑-垂体-肾上腺轴激活和行为抑郁。这些影响主要是在大鼠中研究，使用重组人和小鼠IL-1。由于IL-1 α和IL-1 β在其生物活性的效力方面显示出一些种属特异性，因此本工作的目的是直接比较重组大鼠IL-1 α和IL-1 β在大鼠系统中的作用，作为剖析这些作用所涉及的机制的第一步。在体外，重组大鼠IL-1 α和IL-1 β以与人IL-1相同的亲和力结合到主要表达I型IL-1受体的大鼠胰岛素瘤Rin m5 F细胞系。这种结合激活了IL-1受体，如通过诱导TNF-α mRNA的合成所示。在体内，重组大鼠IL-1 α和IL-1 β提高体温，增加血浆皮质酮和ACTH水平，并抑制社会行为。当IL-1被中心注射时，所有这些作用都是在比当其被外周施用时低100- 1，000倍的剂量下获得的，表明它们是中心介导的。重组大鼠IL-1 α和IL-1 β的相对效力根据终点和注射途径不同而不同，表明IL-1对脑的各种作用可能涉及不同的机制。
IL-1alpha and IL-1beta have potent effects on the central nervous system resulting in fever, activation of the hypothalamic-pituitary-adrenal axis and behavioural depression. These effects have mainly been studied in rats, using recombinant human and mouse IL-1. Because IL-1alpha and IL-1beta show some species specificity in the potency of their biological activities, the objective of the present work was to directly compare the effects of recombinant rat IL-1alpha and IL-1beta in the rat system as a first step to dissect out the mechanisms that are involved in these effects. In vitro, recombinant rat IL-1alpha and IL-1beta bound with the same affinity as human IL-1 to the rat insulinoma Rin m5F cell line that mainly expresses type I IL-1 receptors. This binding activated IL-1 receptors, as shown by induction of the synthesis of TNF-alpha mRNA. In vivo, recombinant rat IL-1alpha and IL-1beta enhanced body temperature, increased plasma levels of corticosterone and ACTH, and depressed social behaviour. All these effects were obtained at doses 100-1,000 fold lower when IL-1 was injected centrally than when it was administered peripherally, indicating that they are centrally mediated. The relative potencies of recombinant rat IL-1alpha and IL-1beta were not the same depending on the endpoint and the route of injection, indicating that different mechanisms are likely to be involved in the various effects of IL-1 on the brain.