Takao T, Hashimoto K, De Souza E B
Second Department of Internal Medicine, Kochi Medical School, Nankoku, Japan.
Int J Dev Neurosci. 1995 Jun-Jul;13(3-4):167-78. doi: 10.1016/0736-5748(95)00015-9.
Interleukin-1 (IL-1) receptors with kinetics, pharmacological and biochemical characteristics of type I IL-1 receptors have been identified in the mouse neuro-endocrine-immune axis. In the present study, we examined the in-vitro and in-vivo modulation of IL-1 receptors by stress and endotoxin treatment. The treatment of AtT-20 mouse pituitary adenoma cells for 24 hr with neuro-endocrine mediators of stress such as corticotropin releasing factor (CRF) and catecholamine (beta 2 adrenergic) receptor agonists produced a dose-dependent increase in cAMP and [125I]IL-1 alpha binding. In contrast, somatostatin and dexamethasone significantly inhibited CRF-stimulated cAMP production and decreased both basal and CRF-mediated increase of [125I]IL-1 alpha binding. Furthermore, in keeping with the effects of stress mediators to upregulate IL-1 receptors in AtT-20 cells, ether-laparotomy stress in mice resulted in a significant increase in [125I]IL-1 alpha binding in the pituitary with no significant alterations observed in the brain; in contrast, [125I]oCRF binding in the pituitary was significantly decreased after the ether-laparotomy stress. Next, we investigated the modulation of IL-1 beta levels and [125I]IL-1 alpha binding following endotoxin lipopolysaccharide (LPS) treatment. IL-1 beta levels were dramatically increased in the peripheral tissues (pituitary, testis and spleen) at 2-6 hr after a single LPS injection (30 micrograms LPS/mouse). However, no significant changes were observed in brain (hippocampus and hypothalamus). [125I]IL-1 alpha binding in the pituitary gland, liver, spleen and testis was significantly decreased at 2 hr following a single administration of both low (30 micrograms LPS/mouse) and high (300 micrograms LPS/mouse) doses of endotoxin. [125I]IL-1 alpha binding in the hippocampus was not significantly altered at 2 hr by a low dose of LPS and was significantly decreased by high dose administration of LPS (300 micrograms/mouse). Following two LPS injections (at 0 and 12 hr), dramatic increases in IL-1 beta concentrations in the hypothalamus, hippocampus, spleen and testis were observed at 2 hr after the second LPS injection; a small but statistically nonsignificant change was evident in the pituitary. Moreover, dramatic decreases in [125I]IL-1 alpha binding were seen after two injections of 30 micrograms LPS/mouse in both central and peripheral tissues. These data provide further support for a role for IL-1 in co-ordinating neuro-endocrine-immune responses to stress and infection.
在小鼠神经 - 内分泌 - 免疫轴中已鉴定出具有I型白细胞介素 -1（IL -1）受体动力学、药理学和生化特性的IL -1受体。在本研究中，我们检测了应激和内毒素处理对IL -1受体的体外和体内调节作用。用应激的神经 - 内分泌介质如促肾上腺皮质激素释放因子（CRF）和儿茶酚胺（β2肾上腺素能）受体激动剂处理AtT -20小鼠垂体腺瘤细胞24小时，可使环磷酸腺苷（cAMP）和[125I]IL -1α结合呈剂量依赖性增加。相反，生长抑素和地塞米松显著抑制CRF刺激的cAMP产生，并降低基础和CRF介导的[125I]IL -1α结合增加。此外，与应激介质上调AtT -20细胞中IL -1受体的作用一致，小鼠乙醚剖腹应激导致垂体中[125I]IL -1α结合显著增加，而脑中未观察到显著变化；相反，乙醚剖腹应激后垂体中[125I]oCRF结合显著降低。接下来，我们研究了内毒素脂多糖（LPS）处理后IL -1β水平和[125I]IL -1α结合的调节情况。单次注射LPS（30微克LPS/小鼠）后2 - 6小时，外周组织（垂体、睾丸和脾脏）中IL -1β水平显著升高。然而，脑（海马和下丘脑）中未观察到显著变化。单次给予低剂量（30微克LPS/小鼠）和高剂量（300微克LPS/小鼠）内毒素后2小时，垂体、肝脏、脾脏和睾丸中的[125I]IL -1α结合显著降低。低剂量LPS处理2小时后，海马中的[125I]IL -1α结合无显著变化，高剂量LPS（300微克/小鼠）给药后显著降低。两次注射LPS（0小时和12小时）后，第二次注射LPS后2小时，下丘脑、海马、脾脏和睾丸中的IL -1β浓度显著升高；垂体中有微小但无统计学意义的变化。此外，两次注射30微克LPS/小鼠后，中枢和外周组织中的[125I]IL -1α结合均显著降低。这些数据为IL -1在协调对应激和感染的神经 - 内分泌 - 免疫反应中的作用提供了进一步支持。
