Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, Boston, Massachusetts, USA.
Department of Neurology and Experimental Neurology, Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Nat Neurosci. 2017 Nov;20(11):1549-1559. doi: 10.1038/nn.4643. Epub 2017 Sep 18.
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.
急性脊髓损伤 (SCI) 导致全身免疫抑制和危及生命的感染，据认为这是由于去甲肾上腺素过度激活和通过下丘脑-垂体-肾上腺轴刺激释放过多的糖皮质激素所致。我们报告称，与低胸段（Th9）SCI 相比，在小鼠急性 SCI 中，尽管促肾上腺皮质激素受到抑制，但会诱导血清去甲肾上腺素抑制和皮质醇同时升高，表明存在原发性（肾上腺）皮质醇增多症。在高胸段（Th1）SCI 中断肾上腺神经支配后，这种神经源性效应更为明显。预防性肾上腺切除术可完全预防 SCI 引起的皮质醇过多和淋巴细胞耗竭，但不能预防肺炎。当肾上腺切除的小鼠被移植去神经的肾上腺以恢复生理皮质醇水平时，动物完全免受肺炎的影响。这些发现确定了 SCI 后介导免疫抑制的适应性交感神经-神经内分泌肾上腺反射，这意味着在 SCI 患者中治疗性纠正皮质醇和儿茶酚胺失衡可能是预防有害感染的一种策略。
