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

Short Title:
Model System:
SCI
Reference Type:
Journal Article
Accession No.:
Journal:
Nature Neuroscience
Year, Volume, Issue, Page(s):
2017, vol. 20, issue 11, pp 1549-1559
Publication Website:
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.
Author(s):
Prüss H, MD, Tedeschi, A, PhD, Thiriot A, PhD, Lynch L, PhD, Loughhead SM, PhD, Stutte S, PhD, Mazo IB, PhD, Kopp MA, MD, Brommer B, PhD, Blex C, PhD, Geurtz LC, MD, Liebscher T, MD, Niedeggen A, MD, Dirnagl U, MD, Bradke F, PhD, Volz MS, MD, DeVivo MJ, PhD, Chen Y, MD PhD, von Andrian UH, MD PhD, Schwab JM, MD PhD
Author Address(es):

Some items may be available for document delivery from the National Rehabilitation Information Center. Make a note of the title and any accession number and contact NARIC at 800-346-2742 to request a copy. There is a charge for document delivery from the NARIC collection.