Kusnecov A W, Rossi-George A
Department of Psychology, Biopsychology and Behavioral Neuroscience Program, Rutgers University, Piscataway, NJ 08855, USA.
Neuroimmunomodulation. 2001;9(2):109-18. doi: 10.1159/000049014.
Activation of the hypothalamic-pituitary-adrenal (HPA) axis is a primary effect of interleukin-1 (IL-1), with elevated glucocorticoids considered a mechanism for negative feedback immunoregulation. However, there is little direct evidence of such a functional relationship between IL-1-mediated immunoregulation and neuroendocrine influences elicited by IL-1. Therefore, the goal of this study was to examine whether the known adjuvant effects of IL-1 are altered in the absence of neuroendocrine feedback due to adrenalectomy.
Male BALB/c mice subjected to adrenalectomy (ADX) or sham surgery were administered with saline or recombinant human IL-1beta (rhIL-1beta) and at the same time immunized with 100 microg ovalbumin (OVA). In vivo and in vitro measures of antigen-specific IgG antibody production, IL-6 production and spleen cell proliferation were taken 6 and 12 days later.
It was demonstrated that administration of rhIL-1beta at a dose that activates the HPA axis resulted in a significant augmentation of serum anti- OVA IgG antibody levels. Interestingly, this augmentation was potentiated in ADX animals. In addition, the in vitro spleen cell memory IgG antibody response to OVA was significantly augmented in rhIL-1beta-treated animals, and again, further potentiated in ADX animals. Interestingly, while hrIL-1beta treatment augmented antigen-stimulated IL-6 production - suggesting an effect of IL-1 on antigen-specific T helper 2 cell memory formation - potentiation was not evident in ADX animals.
These results are consistent with the concept of HPA axis-mediated neuroendocrine feedback on excessive immune responsiveness due to IL-1. Such feedback may prevent disturbances to the self-limiting functions of the immune system, which are important to the prevention of autoimmune diseases, some of which involve elevated IL-1 production.
下丘脑 - 垂体 - 肾上腺（HPA）轴的激活是白细胞介素 -1（IL -1）的主要作用，糖皮质激素升高被认为是负反馈免疫调节的一种机制。然而，关于IL -1介导的免疫调节与IL -1引发的神经内分泌影响之间这种功能关系的直接证据很少。因此，本研究的目的是探讨在肾上腺切除导致神经内分泌反馈缺失的情况下，IL -1已知的佐剂效应是否会改变。
对接受肾上腺切除术（ADX）或假手术的雄性BALB/c小鼠给予生理盐水或重组人IL -1β（rhIL -1β），同时用100微克卵清蛋白（OVA）进行免疫。在6天和12天后进行体内和体外抗原特异性IgG抗体产生、IL -6产生及脾细胞增殖的检测。
结果表明，以激活HPA轴的剂量给予rhIL -1β会导致血清抗OVA IgG抗体水平显著升高。有趣的是，这种升高在ADX动物中更明显。此外，在rhIL -1β处理的动物中，体外脾细胞对OVA的记忆IgG抗体反应显著增强，并且在ADX动物中再次进一步增强。有趣的是，虽然hrIL -1β处理增强了抗原刺激的IL -6产生——表明IL -1对抗原特异性辅助性T细胞2型记忆形成有影响——但在ADX动物中这种增强并不明显。
这些结果与HPA轴介导的对因IL -1导致的过度免疫反应的神经内分泌反馈概念一致。这种反馈可能防止对免疫系统自我限制功能的干扰，这对预防自身免疫性疾病很重要，其中一些自身免疫性疾病涉及IL -1产生升高。
