致热免疫调节剂对体外完整大鼠下丘脑促肾上腺皮质激素释放因子-41和前列腺素E2释放的影响。

Effects of pyrogenic immunomodulators on the release of corticotrophin-releasing factor-41 and prostaglandin E2 from the intact rat hypothalamus in vitro.

作者信息

Milton N G, Self C H, Hillhouse E W

机构信息

Department of Clinical Biochemistry, University of Newcastle upon Tyne.

出版信息

Br J Pharmacol. 1993 May;109(1):88-93. doi: 10.1111/j.1476-5381.1993.tb13535.x.

DOI:10.1111/j.1476-5381.1993.tb13535.x

PMID:8495249

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2175569/

Abstract

The actions of the following pyrogens: lipopolysaccharide (LPS), polyinosinic:polycytidylic acid (Poly-I:C), human interleukin (IL)-1 alpha and IL-1 beta, human IL-6 and rat interferon (INF) on corticotrophin-releasing factor-41 (CRF-41) and prostaglandin E2 (PGE2) release from the intact rat hypothalamus in vitro have been studied. 2. Rat hypothalami were incubated in vitro in an artificial cerebrospinal fluid. Immunoreactive (ir)-CFR-41 and PGE2 released into the medium were measured by two-site enzyme amplified immunometric assay (EAIA) and radioimmunoassay (RIA) respectively. 3. Human IL-6 (1 to 10,000 IU ml-1) caused a dose-dependent release of irCRF-41, rising to a maximal 3-4 fold increase over basal at the highest dose tested. Human IL-1 alpha (1 to 1000 IU ml-1), human IL-1 beta (1 to 1000 IU ml-1), poly-I:C (10 pg ml-1 to 100 micrograms ml-1) and rat INF (1 to 10,000 IRu ml-1) all failed to alter irCRF-41 release. 4. LPS (1 mg ml-1) caused a 35% decrease in irCRF-41 release; however, over the dose-range of 0.1 microgram ml-1 to 100 micrograms ml-1, LPS failed to alter irCRF-41 release. The decreased irCRF-41 release in response to LPS (1 mg ml-1) was accompanied by a decrease in the subsequent 56 mM KCl stimulation of irCRF-41. 5. Human IL-1 alpha and IL-1 beta (1000 IU ml-1) were able to stimulate the release of irPGE2 from intact hypothalami, causing a 2 fold increase over basal release. Poly-I:C (100 microg ml-1), LPS (0.1 microg ml-1 to 1 mg ml-1), rat INF (10,000 IRu ml-1) and human IL-6 (1 to 10,000 iu ml-1) all failed to alter irPGE2release.6. In conclusion, these results suggest that the in vitro release of CRF-41 and PGE2, in response to pyrogens, are mediated via different cytokines. In view of this it is possible that different cytokines may mediate the temperature, prostaglandin and hypothalamo-pituitary-adrenocortical axis activation seen during pyrogenic stimulation in vivo.

摘要

研究了以下几种致热原：脂多糖（LPS）、聚肌苷酸:聚胞苷酸（Poly-I:C）、人白细胞介素（IL）-1α和IL-1β、人IL-6以及大鼠干扰素（INF）对体外完整大鼠下丘脑促肾上腺皮质激素释放因子-41（CRF-41）和前列腺素E2（PGE2）释放的作用。2. 将大鼠下丘脑在人工脑脊液中进行体外孵育。分别通过双位点酶放大免疫测定法（EAIA）和放射免疫测定法（RIA）测量释放到培养基中的免疫反应性（ir）-CFR-41和PGE2。3. 人IL-6（1至10,000 IU/ml）引起irCRF-41的剂量依赖性释放，在测试的最高剂量下比基础值最大增加3至4倍。人IL-1α（1至1000 IU/ml）、人IL-1β（1至1000 IU/ml）、Poly-I:C（10 pg/ml至100μg/ml）和大鼠INF（1至10,000 IRu/ml）均未改变irCRF-41的释放。4. LPS（1 mg/ml）使irCRF-41释放减少35%；然而，在0.1μg/ml至100μg/ml的剂量范围内，LPS未能改变irCRF-41的释放。对LPS（1 mg/ml）反应时irCRF-41释放的减少伴随着随后56 mM KCl刺激的irCRF-41的减少。5. 人IL-1α和IL-1β（1000 IU/ml）能够刺激完整下丘脑释放irPGE2，使其比基础释放增加2倍。Poly-I:C（100μg/ml）、LPS（0.1μg/ml至1 mg/ml）、大鼠INF（10,000 IRu/ml）和人IL-6（1至10,000 iu/ml）均未改变irPGE2的释放。6. 总之，这些结果表明，CRF-41和PGE2对致热原的体外释放是由不同的细胞因子介导的。鉴于此，在体内致热原刺激过程中观察到的不同细胞因子可能介导体温、前列腺素和下丘脑-垂体-肾上腺皮质轴的激活。