Ohgo S, Nakatsuru K, Ishikawa E, Matsukura S
Department of Medicine, Miyazaki Medical College, Japan.
Brain Res. 1991 Sep 6;558(2):217-23. doi: 10.1016/0006-8993(91)90771-m.
We demonstrated previously that interleukin-1 (IL-1) (recombinant human IL-1 alpha and -1 beta) stimulated the release of corticotropin-releasing factor (CRF) from the superfused rat hypothalamo-neurohypophyseal complex (HNC), independently of the cholinergic system. In the present study we studied the effects of IL-1 on the release of CRF not only from the HNC but also from the isolated hypothalamus of rats in a superfusion system to define the origin of measured CRF and the site of IL-1 action. We also studied the possible involvement of the histaminergic system in the mediation of the stimulation by IL-1. An increase in CRF was elicited from the HNC and the isolated hypothalamus in a dose-dependent manner by human recombinant IL-1 beta in concentrations of 0.1-10 nM with similar time courses. Histamine in concentrations of 1-100 nM also elicited qualitatively similar increases of CRF from these two types of explants. The increases in CRF release from the HNC induced by 10 nM of histamine were completely suppressed in the combined presence of pyrilamine (10 microM) and cimetidine (10 microM), an H1 and an H2 receptor antagonist, respectively. On the other hand, the increase in CRF release induced by 10 nM IL-1 beta was not affected by the combination of these two antagonists. These results indicate that IL-1 stimulates CRF release from the median eminence through an action on the hypothalamus, and that the stimulatory effect of IL-1 is probably independent of the histaminergic system.
我们先前已证明，白细胞介素-1（IL-1）（重组人IL-1α和-1β）可刺激来自体外灌流大鼠下丘脑-神经垂体复合体（HNC）的促肾上腺皮质激素释放因子（CRF）释放，且不依赖于胆碱能系统。在本研究中，我们不仅研究了IL-1对HNC释放CRF的影响，还研究了其对超灌流系统中大鼠离体下丘脑释放CRF的影响，以确定所测CRF的来源及IL-1的作用位点。我们还研究了组胺能系统在介导IL-1刺激作用中可能的参与情况。人重组IL-1β以0.1 - 10 nM的浓度可使HNC和离体下丘脑以剂量依赖方式引发CRF增加，且时间进程相似。1 - 100 nM浓度的组胺也可使这两种类型的外植体引发性质相似的CRF增加。10 nM组胺诱导的HNC中CRF释放增加在分别存在H1受体拮抗剂吡苄明（10 μM）和H2受体拮抗剂西咪替丁（10 μM）时被完全抑制。另一方面，10 nM IL-1β诱导的CRF释放增加不受这两种拮抗剂联合使用的影响。这些结果表明，IL-1通过作用于下丘脑刺激正中隆起释放CRF，且IL-1的刺激作用可能独立于组胺能系统。
