Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex
Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex
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DOI：
10.1038/nn.4643
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发表时间：
2017-11-01
影响因子：
25
通讯作者：
Schwab, Jan M.
中科院分区：
文献类型：
--
作者：
Pruess, Harald;Tedeschi, Andrea;Schwab, Jan M.
急性脊髓损伤（SCI）引起全身免疫抑制和危及生命的感染，被认为是由去甲肾上腺素能过度激活和通过下丘脑-垂体-肾上腺轴刺激过量糖皮质激素释放引起的。而不是连续的下丘脑-垂体-肾上腺轴激活，我们报告说，急性脊髓损伤小鼠诱导抑制血清去甲肾上腺素和伴随的皮质醇增加，尽管抑制促肾上腺皮质激素，表明原发性（肾上腺）皮质醇增多症。与低胸水平（Th 9）SCI相比，高胸水平（Th 1）SCI切断肾上腺神经支配后，这种神经原性效应更为明显。预防性肾上腺切除术完全防止SCI诱导的糖皮质激素过多和淋巴细胞耗竭，但不能预防肺炎。当切除肾上腺的小鼠移植去神经支配的肾上腺以恢复生理性糖皮质激素水平时，动物完全免于肺炎。这些研究结果确定了一个适应不良的交感神经-神经内分泌肾上腺反射介导的免疫抑制SCI后，这意味着治疗SCI患者的糖皮质激素和儿茶酚胺失衡的正常化可能是一种策略，以防止有害的感染。
Acute spinal cord injury (SCI) causes systemic immunosuppression and life-threatening infections, thought to result from noradrenergic overactivation and excess glucocorticoid release via hypothalamus-pituitary-adrenal axis stimulation. Instead of consecutive hypothalamus-pituitary-adrenal axis activation, we report that acute SCI in mice induced suppression of serum norepinephrine and concomitant increase in cortisol, despite suppressed adrenocorticotropic hormone, indicating primary (adrenal) hypercortisolism. This neurogenic effect was more pronounced after high-thoracic level (Th1) SCI disconnecting adrenal gland innervation, compared with low-thoracic level (Th9) SCI. Prophylactic adrenalectomy completely prevented SCI-induced glucocorticoid excess and lymphocyte depletion but did not prevent pneumonia. When adrenalectomized mice were transplanted with denervated adrenal glands to restore physiologic glucocorticoid levels, the animals were completely protected from pneumonia. These findings identify a maladaptive sympathetic-neuroendocrine adrenal reflex mediating immunosuppression after SCI, implying that therapeutic normalization of the glucocorticoid and catecholamine imbalance in SCI patients could be a strategy to prevent detrimental infections.