Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex

被引：135

作者：

Pruess, Harald ^{[1
,2
,3
,4
,5
]}

Tedeschi, Andrea ^{[6
,7
,8
]}

Thiriot, Aude ^{[1
]}

Lynch, Lydia ^{[1
]}

Loughhead, Scott M. ^{[1
]}

Stutte, Susanne ^{[1
,9
]}

Mazo, Irina B. ^{[1
]}

Kopp, Marcel A. ^{[2
,3
,4
]}

Brommer, Benedikt ^{[2
,3
,4
,6
]}

Blex, Christian ^{[2
,3
,4
]}

Geurtz, Laura-Christin ^{[2
,3
,4
]}

Liebscher, Thomas ^{[10
]}

Niedeggen, Andreas ^{[10
]}

Dirnagl, Ulrich ^{[2
,3
,4
,5
]}

Bradke, Frank ^{[7
]}

Volz, Magdalena S. ^{[11
]}

DeVivo, Michael J. ^{[12
]}

Chen, Yuying ^{[12
]}

von Andrian, Ulrich H. ^{[1
]}

Schwab, Jan M. ^{[2
,3
,4
,13
]}

机构：

[1] Harvard Med Sch, Div Immunol, Dept Microbiol & Immunobiol, Boston, MA 02115 USA

[2] Charite Univ Med Berlin, Dept Neurol & Expt Neurol, Clin & Expt Spinal Cord Injury Res Neuroparaplegi, Berlin, Germany

[3] Humboldt Univ, Free Univ Berlin, Berlin, Germany

[4] Berlin Inst Hlth, Berlin, Germany

[5] German Ctr Neurodegenerat Dis DZNE, Berlin, Germany

[6] Harvard Med Sch, Ctr Life Sci, Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA USA

[7] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany

[8] Ohio State Univ, Wexner Med Ctr, Ctr Brain & Spinal Cord Repair, Dept Neurosci,Neurol Inst, Columbus, OH 43210 USA

[9] Ludwig Maximilians Univ Munchen, Biomed Ctr, Inst Immunol, Martinsried, Germany

[10] Trauma Hosp Berlin, Treatment Ctr Spinal Cord Injuries, Berlin, Germany

[11] Charite Univ Med Berlin, Dept Gastroenterol Infectiol & Rheumatol, Berlin, Germany

[12] Univ Alabama Birmingham, Dept Phys Med & Rehabil, Natl Spinal Cord Injury Stat Ctr, Birmingham, AL USA

[13] Ohio State Univ, Ctr Brain & Spinal Cord Repair, Dept Phys Med & Rehabil, Dept Neurol & Neurosci,Wexner Med Ctr,Neurol Inst, Columbus, OH USA

来源：

NATURE NEUROSCIENCE | 2017年 / 20卷 / 11期

关键词：

IMMUNE-DEFICIENCY SYNDROME; NERVOUS-SYSTEM; STRESS HORMONES; INNERVATION; LEVEL; INFECTIONS; STROKE; SPLEEN; INFLAMMATION; RESPONSES;

D O I：

10.1038/nn.4643

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：1549 / +

页数：13

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