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

Harald Prüss, Andrea Tedeschi, Aude Thiriot, Lydia Lynch, Scott M. Loughhead, Susanne Stutte, Irina B. Mazo, Marcel A. Kopp, Benedikt Brommer, Christian Blex, Laura Christin Geurtz, Thomas Liebscher, Andreas Niedeggen, Ulrich Dirnagl, Frank Bradke, Magdalena S. Volz, Michael J. DeVivo, Yuying Chen, Ulrich H. Von Andrian, Jan M. Schwab

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1549-1559
Number of pages11
JournalNature neuroscience
Volume20
Issue number11
DOIs
StatePublished - 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Neuroscience

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