Raber J, Bloom F E
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
J Neurosci. 1994 Oct;14(10):6187-95. doi: 10.1523/JNEUROSCI.14-10-06187.1994.
The neuropeptide arginine vasopressin (AVP) can replace the cytokine interleukin 2 (IL-2) as a T-cell mitogen for the induction of interferon gamma (IFN gamma) expression in splenic cultures. IL-2-like and IL-2 receptor immunoreactivity have been reported in different brain regions, under normal and pathophysiological conditions. Regulatory functions for IL-2 in the CNS have been suggested. In addition to the spleen, AVP might also mediate some IL-2 effects centrally. In the present study, we evaluated the effect of IL-2 on the in vitro release of AVP from the hypothalamus and amygdala. In addition, we used these release systems to study the possible involvement of NO-mediated signaling in AVP release, based on the reported detection of nitric oxide synthase (NOS) in the hypothalamus and amygdala. IL-2 rapidly stimulates AVP release in both regions, in a calcium- and dose-dependent manner. In addition, nitroprusside also induces AVP release. Norepinephrine also induces AVP release from both the hypothalamus, as well as the amygdala. The norepinephrine-induced AVP release is antagonized by phentolamine, but not by propranolol, suggesting an alpha-adrenergic receptor-mediated AVP response in both brain regions. The IL-2- and acetylcholine-induced AVP release is antagonized by Ng-methyl-L-arginine, indicating a role for NO in this AVP release. Ng-methyl-L-arginine does not affect the norepinephrine-induced AVP release. A stimulatory effect of IL-2 on hypothalamic CRF release and plasma ACTH has already been reported. Our results suggest that in addition to CRF, AVP may also mediate the IL-2 stimulation of ACTH secretion. These data further suggest that in addition to the hypothalamus, the amygdala may also play a role in the bidirectional communication between neuroendocrine and immune systems. Understanding the mode of interaction between IL-2 with AVP could clarify the pathophysiologic or toxic effects of high brain levels of IL-2.
神经肽精氨酸加压素（AVP）可替代细胞因子白细胞介素2（IL-2）作为T细胞丝裂原，用于诱导脾细胞培养物中γ干扰素（IFNγ）的表达。在正常和病理生理条件下，已报道在不同脑区存在IL-2样和IL-2受体免疫反应性。已有人提出IL-2在中枢神经系统中具有调节功能。除脾脏外，AVP可能也在中枢介导一些IL-2的作用。在本研究中，我们评估了IL-2对下丘脑和杏仁核体外释放AVP的影响。此外，基于已报道的下丘脑和杏仁核中一氧化氮合酶（NOS）的检测结果，我们利用这些释放系统研究了NO介导的信号传导在AVP释放中的可能作用。IL-2以钙和剂量依赖性方式快速刺激这两个区域的AVP释放。此外，硝普钠也可诱导AVP释放。去甲肾上腺素也可诱导下丘脑和杏仁核释放AVP。酚妥拉明可拮抗去甲肾上腺素诱导的AVP释放，但普萘洛尔则不能，这表明在这两个脑区中，AVP反应是由α-肾上腺素能受体介导的。N-甲基-L-精氨酸可拮抗IL-2和乙酰胆碱诱导的AVP释放，表明NO在这种AVP释放中发挥作用。N-甲基-L-精氨酸不影响去甲肾上腺素诱导的AVP释放。已有报道称IL-2对下丘脑促肾上腺皮质激素释放因子（CRF）释放和血浆促肾上腺皮质激素（ACTH）有刺激作用。我们的结果表明，除CRF外，AVP可能也介导IL-2对ACTH分泌的刺激作用。这些数据进一步表明，除下丘脑外，杏仁核可能也在神经内分泌和免疫系统之间的双向通信中发挥作用。了解IL-2与AVP之间的相互作用模式可能有助于阐明脑内高浓度IL-2的病理生理或毒性作用。
