Hodgson D M, Yirmiya R, Chiappelli F, Taylor A N
Department of Neurobiology and Brain Research Institute, School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Brain Res. 1999 Jan 16;816(1):200-8. doi: 10.1016/s0006-8993(98)01185-8.
Interleukin-1beta (IL-1beta) is released within the brain following stress, trauma, infection, and in specific brain disorders. This centrally acting IL-1beta has recently been shown to impair peripheral immunity. Central administration of IL-1beta suppresses natural killer (NK) cell activity impairs lung clearance of tumor cells and enhances tumor colonization. Using an in vivo model of tumor colonization (lung clearance of NK-sensitive MADB106 adenocarcinoma cells), this study examined the role of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) in mediating these effects. We demonstrate that adrenalectomy significantly attenuated the impaired lung clearance of MADB106 tumor cells induced by intracerebroventricular (i.c.v.) administration of IL-1beta (20 ng). Supplementing adrenalectomized animals with corticosterone did not reinstate the effect. The effect of IL-1beta on lung clearance was blocked by pretreatment with the beta-adrenergic antagonist, nadolol (0.5 mg/kg), but not by the alpha-antagonist phentolamine (5 mg/kg). Peripheral noradrenergic pathways are not implicated given that systemic administration of the noradrenergic neurotoxin, 6-hydroxydopamine, did not block the effect of IL-1beta. Taken together, these findings indicate that IL-1beta impairs lung clearance of MADB106 tumor cells via the actions of adrenal catecholamines, most likely epinephrine, acting at beta-adrenergic receptors in the periphery.
白细胞介素-1β（IL-1β）在应激、创伤、感染以及特定脑部疾病发生时会在脑内释放。最近研究表明，这种作用于中枢的IL-1β会损害外周免疫。脑室内注射IL-1β会抑制自然杀伤（NK）细胞活性，损害肺部对肿瘤细胞的清除能力，并促进肿瘤定植。本研究利用肿瘤定植的体内模型（对NK敏感的MADB106腺癌细胞的肺部清除），探讨下丘脑-垂体-肾上腺（HPA）轴和交感神经系统（SNS）在介导这些效应中的作用。我们发现，肾上腺切除可显著减轻脑室内注射20 ng IL-1β所诱导的MADB106肿瘤细胞肺部清除受损。给肾上腺切除的动物补充皮质酮并不能恢复该效应。β-肾上腺素能拮抗剂纳多洛尔（0.5 mg/kg）预处理可阻断IL-1β对肺部清除的影响，而α-拮抗剂酚妥拉明（5 mg/kg）则不能。鉴于去甲肾上腺素能神经毒素6-羟基多巴胺的全身给药并未阻断IL-1β的效应，外周去甲肾上腺素能途径未参与其中。综上所述，这些发现表明，IL-1β通过肾上腺儿茶酚胺（很可能是肾上腺素）作用于外周的β-肾上腺素能受体，从而损害MADB106肿瘤细胞的肺部清除。
