Johnson J D, Campisi J, Sharkey C M, Kennedy S L, Nickerson M, Greenwood B N, Fleshner M
Department of Integrative Physiology and Center for Neuroscience, Clare Small Building, Room #114, University of Colorado, Boulder, CO 80309-0354, USA.
Neuroscience. 2005;135(4):1295-307. doi: 10.1016/j.neuroscience.2005.06.090. Epub 2005 Sep 13.
Proinflammatory cytokines act at receptors in the CNS to alter physiological and behavioral responses. Exposure to stressors increases both peripheral and central proinflammatory cytokines, yet the mechanism(s) of induction remain unknown. Experiments here examined the role of catecholamines in the in vivo induction of proinflammatory cytokines following tailshock stress. Rats were pretreated i.p. with 2.0 mg/kg prazosin (alpha1-adrenoceptor antagonist), 10.0 mg/kg propranolol (beta-adrenoceptor antagonist), or 5.0 mg/kg labetalol (alpha1- and beta-adrenoceptor antagonist) 30 min prior to tailshock exposure and plasma interleukin-1beta (IL-1beta) and IL-6, along with tissue interleukin-1beta from the hypothalamus, hippocampus, and pituitary were measured immediately following stressor termination. Prazosin attenuated stress-induced plasma IL-1beta and IL-6, but had no effect on tissue IL-1beta levels, while propranolol attenuated plasma IL-6 and blocked tissue IL-1beta elevation, and labetalol, which cannot cross the blood-brain barrier, attenuated plasma IL-1beta and IL-6, blocked pituitary IL-1beta, but had no effect on central tissue IL-1beta levels. Furthermore, administration of 50.0 mg/kg N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride, a neurotoxin that lesions neural projections from the locus coeruleus, prevented stress-induced elevation in hippocampal IL-1beta, a region highly innervated by the locus coeruleus, but had no effect on hypothalamic IL-1beta, a region that receives few locus coeruleus projections. Finally, i.p. injection of 5.0 mg/kg isoproterenol (beta-adrenoceptor agonist) was sufficient to induce circulating IL-1 and IL-6, and tissue IL-1beta. These data suggest catecholamines play an important role in the induction of stress-induced proinflammatory cytokines and that beta-adrenoceptors are critical for tissue IL-1beta induction, while both alpha- and beta-adrenoceptors contribute to the induction of plasma cytokines.
促炎细胞因子作用于中枢神经系统的受体，以改变生理和行为反应。暴露于应激源会增加外周和中枢促炎细胞因子，但诱导机制仍不清楚。本实验研究了儿茶酚胺在尾部电击应激后体内促炎细胞因子诱导中的作用。在尾部电击暴露前30分钟，给大鼠腹腔注射2.0mg/kg哌唑嗪（α1-肾上腺素能受体拮抗剂）、10.0mg/kg普萘洛尔（β-肾上腺素能受体拮抗剂）或5.0mg/kg拉贝洛尔（α1和β-肾上腺素能受体拮抗剂），应激源终止后立即测量血浆白细胞介素-1β（IL-1β）和IL-6，以及下丘脑、海马和垂体的组织白细胞介素-1β。哌唑嗪减轻了应激诱导的血浆IL-1β和IL-6，但对组织IL-1β水平没有影响，而普萘洛尔减轻了血浆IL-6并阻止了组织IL-1β升高，不能穿过血脑屏障的拉贝洛尔减轻了血浆IL-1β和IL-6，阻止了垂体IL-1β升高，但对中枢组织IL-1β水平没有影响。此外，给予50.0mg/kg N-（2-氯乙基）-N-乙基-2-溴苄胺盐酸盐，一种损伤蓝斑神经投射的神经毒素，可防止应激诱导的海马IL-1β升高，海马是一个受蓝斑高度支配的区域，但对下丘脑IL-1β没有影响，下丘脑接受蓝斑投射较少。最后，腹腔注射5.0mg/kg异丙肾上腺素（β-肾上腺素能受体激动剂）足以诱导循环中的IL-1和IL-6以及组织IL-1β。这些数据表明，儿茶酚胺在应激诱导的促炎细胞因子的诱导中起重要作用，β-肾上腺素能受体对组织IL-1β的诱导至关重要，而α和β-肾上腺素能受体都参与血浆细胞因子的诱导。
