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

doi:10.1038/nn.4643

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 journal › Article › peer-review

125 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 language	English (US)
Pages (from-to)	1549-1559
Number of pages	11
Journal	Nature neuroscience
Volume	20
Issue number	11
DOIs	https://doi.org/10.1038/nn.4643
State	Published - 2017
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Neuroscience

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10.1038/nn.4643

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Prüss, H., Tedeschi, A., 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., Bradke, F., Volz, M. S., DeVivo, M. J., Chen, Y., Von Andrian, U. H., & Schwab, J. M. (2017). Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex. Nature neuroscience, 20(11), 1549-1559. https://doi.org/10.1038/nn.4643

@article{a7d0c8db450d4a78a90f8930bd90992b,

title = "Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex",

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

year = "2017",

doi = "10.1038/nn.4643",

language = "English (US)",

volume = "20",

pages = "1549--1559",

journal = "Nature neuroscience",

issn = "1097-6256",

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Prüss, H, Tedeschi, A, Thiriot, A, Lynch, L, Loughhead, SM, Stutte, S, Mazo, IB, Kopp, MA, Brommer, B, Blex, C, Geurtz, LC, Liebscher, T, Niedeggen, A, Dirnagl, U, Bradke, F, Volz, MS, DeVivo, MJ, Chen, Y, Von Andrian, UH & Schwab, JM 2017, 'Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex', Nature neuroscience, vol. 20, no. 11, pp. 1549-1559. https://doi.org/10.1038/nn.4643

TY - JOUR

T1 - Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex

AU - Prüss, Harald

AU - Tedeschi, Andrea

AU - Thiriot, Aude

AU - Lynch, Lydia

AU - Loughhead, Scott M.

AU - Stutte, Susanne

AU - Mazo, Irina B.

AU - Kopp, Marcel A.

AU - Brommer, Benedikt

AU - Blex, Christian

AU - Geurtz, Laura Christin

AU - Liebscher, Thomas

AU - Niedeggen, Andreas

AU - Dirnagl, Ulrich

AU - Bradke, Frank

AU - Volz, Magdalena S.

AU - DeVivo, Michael J.

AU - Chen, Yuying

AU - Von Andrian, Ulrich H.

AU - Schwab, Jan M.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

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JO - Nature neuroscience

JF - Nature neuroscience

IS - 11

ER -

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

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