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Nat Neurosci. 2017 Nov;20(11):1549-1559. doi: 10.1038/nn.4643. Epub 2017 Sep 18.

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

Author information

1
Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, Boston, Massachusetts, USA.
2
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.
3
German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
4
Boston Children's Hospital, F.M. Kirby Neurobiology Center, Center for Life Science, Harvard Medical School, Boston, Massachusetts, USA.
5
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
6
Center for Brain and Spinal Cord Repair, Department of Neuroscience, The Neurological Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
7
Institute for Immunology, Biomedical Center, Ludwig-Maximilians-University Munich, Martinsried, Germany.
8
Treatment Centre for Spinal Cord Injuries, Trauma Hospital Berlin, Berlin, Germany.
9
Department of Gastroenterology, Infectiology and Rheumatology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
10
National Spinal Cord Injury Statistical Center, Department of Physical Medicine and Rehabilitation, University of Alabama at Birmingham, Birmingham, Alabama, USA.
11
Department of Neurology and Neuroscience, Center for Brain and Spinal Cord Repair, Department of Physical Medicine and Rehabilitation, The Neurological Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Abstract

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.

PMID:
28920935
DOI:
10.1038/nn.4643
[Indexed for MEDLINE]

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