糖皮质激素介导的整合于大脑水平的免疫调节回路:我们的早期研究和现在的观点。

IF 2.2 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Neuroimmunomodulation Pub Date : 2024-01-01 Epub Date: 2024-11-06 DOI:10.1159/000542401
Hugo Besedovsky, Adriana Del Rey
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引用次数: 0

摘要

背景 早在 20 世纪 40 年代,人们就知道糖皮质激素的药理作用可以抑制炎症和免疫过程,这些激素至今仍是治疗含有免疫成分的疾病最广泛使用的治疗工具之一。然而,后来人们逐渐认识到,内源性糖皮质激素既可以支持也可以抑制免疫过程。摘要 早期的研究表明:a)内源性糖皮质激素水平可调节免疫细胞的活性;b)免疫反应本身可刺激下丘脑-垂体-肾上腺(HPA)轴释放糖皮质激素,使其达到可发挥免疫调节作用的水平;c)免疫产物,即后来确定的细胞因子,可介导这种作用。在这些基础上,提出了糖皮质激素介导的免疫调节回路的存在。研究还表明,内源性糖皮质激素水平的升高在感染和其他具有免疫成分的疾病中具有保护作用。然而,在动物模型和人体中发现,在一些与免疫有关的疾病中,这些作用会因多个层面的缺陷而减弱,例如糖皮质激素抵抗或肾上腺功能不全。后来有证据表明,糖皮质激素介导的免疫调节回路也可被细胞因子激活,细胞因子不仅是免疫刺激的结果,也可在心理/感官和物理刺激后产生。因此,这一回路可以在大脑水平上整合,除了刺激 HPA 轴外,细胞因子还可以影响突触可塑性,很可能是通过三方突触,其中作为神经免疫细胞的星形胶质细胞是第三个组成部分。重要信息 糖皮质激素介导的免疫调节回路在维持健康方面发挥着核心作用,这一点现已得到公认。然而,内源性糖皮质激素的疗效会受到多种变量的影响。此外,由于细胞因子和其他免疫产物还具有许多其他神经-内分泌和新陈代谢效应,其他神经-内分泌-免疫回路也可能同时起作用,或在不同的病理过程中起主导作用。对这些方面的考虑可能有助于实施最终减少外源性糖皮质激素治疗剂量的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A Glucocorticoid-Mediated Immunoregulatory Circuit Integrated at Brain Levels: Our Early Studies and a Present View.

Background: It was known since the 1940s that pharmacological administration of glucocorticoids can inhibit inflammatory and immune processes, and these hormones are still today among the most widely used therapeutic tools to treat diseases with immune components. However, it became clear later that endogenous glucocorticoids can either support or restrain immune processes.

Summary: Early studies showed that (a) endogenous levels of glucocorticoids can modulate immune cell activity; (b) the immune response itself can stimulate the hypothalamus-pituitary-adrenal (HPA) axis to release glucocorticoids to levels that can exert immunoregulatory effects; (c) immune products, later identified as cytokines, mediate this effect. On these bases, the existence of a glucocorticoid-mediated immunoregulatory circuit was proposed. It was also shown that increased levels of endogenous glucocorticoids exert protective effects during infections and other diseases with immune components. However, it was found in animal models and in humans that these effects can be blunted in several immune-linked diseases by defects at several levels, for example, by glucocorticoid resistance or by adrenal insufficiency. Evidence was later provided that the glucocorticoid-mediated immunoregulatory circuit can also be activated by cytokines produced not only as consequence of immune stimulation but also following psycho/sensorial and physical stimuli. Thus, this circuit can be integrated at brain levels and, besides stimulating the HPA axis, cytokines can also affect synaptic plasticity, most likely via a tripartite synapse, with astrocytes as neuro-immune cells acting as the third component.

Key messages: It is now well established that the glucocorticoid-mediated immunoregulatory circuit plays a central role in maintaining health. However, several variables can condition the efficacy of the effect of endogenous glucocorticoids. Furthermore, since cytokines and other immune products have many other neuroendocrine and metabolic effects, other neuroendocrine-immune circuits could simultaneously operate or become predominant during different pathologies. The consideration of these aspects might help to implement strategies to eventually decrease therapeutic doses of exogenous glucocorticoids.

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来源期刊
Neuroimmunomodulation
Neuroimmunomodulation 医学-免疫学
CiteScore
3.60
自引率
4.20%
发文量
35
审稿时长
>12 weeks
期刊介绍: The rapidly expanding area of research known as neuroimmunomodulation explores the way in which the nervous system interacts with the immune system via neural, hormonal, and paracrine actions. Encompassing both basic and clinical research, ''Neuroimmunomodulation'' reports on all aspects of these interactions. Basic investigations consider all neural and humoral networks from molecular genetics through cell regulation to integrative systems of the body. The journal also aims to clarify the basic mechanisms involved in the pathogenesis of the CNS pathology in AIDS patients and in various neurodegenerative diseases. Although primarily devoted to research articles, timely reviews are published on a regular basis.
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