Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex.
Harald PrüssAndrea TedeschiAude ThiriotLydia LynchScott M LoughheadSusanne StutteIrina B MazoMarcel A KoppBenedikt BrommerChristian BlexLaura-Christin GeurtzThomas LiebscherAndreas NiedeggenUlrich DirnaglFrank BradkeMagdalena S VolzMichael J DeVivoYuying ChenUlrich H von AndrianJan M SchwabPublished in: Nature neuroscience (2017)
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.
Keyphrases
- spinal cord injury
- spinal cord
- neuropathic pain
- drug induced
- high glucose
- diabetic rats
- respiratory failure
- liver failure
- end stage renal disease
- ejection fraction
- high fat diet induced
- oxidative stress
- intensive care unit
- chronic kidney disease
- prognostic factors
- insulin resistance
- acute respiratory distress syndrome