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

• Published in: Nature neuroscience Vol. 20; no. 11; pp. 1549 - 1559
• Main Authors: 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, von Andrian, Ulrich H, Schwab, Jan M
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2017; Nature Publishing Group
• Subjects: 13/31; 14/34; 631/378/371; 631/553; 64/60; Adrenal glands; Adrenal Glands - immunology; Adrenal Glands - transplantation; Adrenalectomy; Adrenalectomy - adverse effects; Adrenalectomy - methods; Adrenergic mechanisms; Adrenocorticotropic hormone; Adult; Aged; Animal Genetics and Genomics; Animals; Behavioral Sciences; Biological Techniques; Biomedicine; Care and treatment; Catecholamine; Catecholamines; Cortisol; Development and progression; Female; Glucocorticoids; Health aspects; Humans; Hypothalamo-Hypophyseal System - immunology; Hypothalamus; Immune response regulation; Immune Tolerance - immunology; Immunodeficiency; Immunosuppression; Infections; Innervation; Lymphocytes T; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Middle Aged; Neurobiology; Neurosciences; Norepinephrine; Observations; Pituitary; Pituitary-Adrenal System - immunology; Pneumonia; Reflex - immunology; Single-Blind Method; Spinal cord injuries; Spinal Cord Injuries - complications; Spinal Cord Injuries - immunology; Spinal Cord Injuries - surgery; Thoracic Vertebrae - injuries; Thorax
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.4643

Spinal cord injury causes life-threatening infections. The authors report that this is partially mediated by a maladaptive neuroendocrine reflex, extending from the spinal cord to the adrenal glands, where it blocks catecholamines while producing immunosuppressive corticosteroids. The effect depends on the spinal injury level, and normalization of hormones production by the adrenals rescued mice from pneumonia. 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.