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

Prüss, Harald; Tedeschi, Andrea; Thiriot, Aude; Lynch, Lydia; Loughhead, Scott M.; Stutte, Susanne; Mazo, Irina B.; Kopp, Marcel A.; Brommer, Benedikt; Blex, Christian; Geurtz, Laura-Christin; Liebscher, Thomas; Niedeggen, Andreas; Dirnagl, Ulrich; Bradke, Frank; Volz, Magdalena S.; DeVivo, Michael J.; Chen, Yuying; Andrian, Ulrich H. von und Schwab, Jan M. (2017): Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex. In: Nature Neuroscience, Bd. 20, Nr. 11: S. 1549-1559

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1097-6256
• Sprache: Englisch