Journal Article

DZNE-2020-05904

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex.

Prüss, H. (First author)DZNE* ; Tedeschi, A.DZNE* ; Thiriot, A. ; Lynch, L. ; Loughhead, S. M. ; Stutte, S. ; Mazo, I. B. ; Kopp, M. A. ; Brommer, B. ; Blex, C. ; Geurtz, L.-C. ; Liebscher, T. ; Niedeggen, A. ; Dirnagl, U.DZNE* ; Bradke, F.DZNE* ; Volz, M. S. ; DeVivo, M. J. ; Chen, Y. ; von Andrian, U. H. (Corresponding author) ; Schwab, J. M.

2017
Nature Publ. Group58142 London

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Please use a persistent id in citations: doi:10.1038/nn.4643

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.

Keyword(s): Adrenal Glands: immunology (MeSH) ; Adrenal Glands: transplantation (MeSH) ; Adrenalectomy: adverse effects (MeSH) ; Adrenalectomy: methods (MeSH) ; Adult (MeSH) ; Aged (MeSH) ; Animals (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Hypothalamo-Hypophyseal System: immunology (MeSH) ; Immune Tolerance: immunology (MeSH) ; Male (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Knockout (MeSH) ; Mice, Transgenic (MeSH) ; Middle Aged (MeSH) ; Pituitary-Adrenal System: immunology (MeSH) ; Reflex: immunology (MeSH) ; Single-Blind Method (MeSH) ; Spinal Cord Injuries: complications (MeSH) ; Spinal Cord Injuries: immunology (MeSH) ; Spinal Cord Injuries: surgery (MeSH) ; Thoracic Vertebrae: injuries (MeSH)

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Contributing Institute(s):

1. Autoimmune Enzephalopathies (AG Prüß)
2. Axon Growth and Regeneration (AG Bradke)
3. Vascular Pathology (AG Dirnagl ; AG Dirnagl)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)
2. 341 - Molecular Signaling (POF3-341) (POF3-341)
3. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2017

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Database coverage:
; BIOSIS Previews ; BIOSIS Reviews Reports And Meetings ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 30 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection

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