Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany.
J Neuroimmunol. 2010 Feb 26;219(1-2):75-80. doi: 10.1016/j.jneuroim.2009.12.001. Epub 2010 Jan 19.
The neurotransmitter noradrenaline (NA) plays a pivotal role in immune regulation. Here we used the selective neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) to investigate the impact of central NA depletion on cytokine production by splenic monocytes/macrophages and T cells. Intraperitoneal administration of DSP-4 in adult rats induced a substantial reduction of noradrenergic neurons in the locus coeruleus and the A5 cell group. The degeneration of brainstem noradrenergic neurons was accompanied by a significant decrease in the production of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha by lipopolysaccharide-stimulated splenocytes. In addition, upon T cell receptor stimulation with anti-CD3, isolated splenocytes of DSP-4 treated animals produced significantly less interferon (IFN)-gamma but not IL-2 and IL-4. The proportion of monocytes/macrophages and T cells in the spleen remained unaffected by the neurotoxin treatment, however, the percentage of natural killer cells decreased significantly. The findings suggest that a certain level of central noradrenergic tone is required for normal functioning of peripheral immune cells.
神经递质去甲肾上腺素（NA）在免疫调节中起着关键作用。在这里，我们使用选择性神经毒素 N-(2-氯乙基)-N-乙基-2-溴苯甲胺（DSP-4）来研究中枢去甲肾上腺素耗竭对脾单核细胞/巨噬细胞和 T 细胞细胞因子产生的影响。DSP-4 腹腔内给药可诱导成年大鼠蓝斑和 A5 细胞群中的去甲肾上腺素能神经元大量减少。脑干去甲肾上腺素能神经元的退化伴随着脂多糖刺激的脾细胞产生的白细胞介素 (IL)-1β、IL-6 和肿瘤坏死因子 (TNF)-α显著减少。此外，在用抗 CD3 刺激 T 细胞受体时，用 DSP-4 处理的动物的分离脾细胞产生的干扰素 (IFN)-γ显著减少，但不产生 IL-2 和 IL-4。神经毒素处理对脾中单核细胞/巨噬细胞和 T 细胞的比例没有影响，但是自然杀伤细胞的百分比显著下降。这些发现表明外周免疫细胞的正常功能需要一定水平的中枢去甲肾上腺素张力。
