CENTRAL NERVOUS SYSTEM INJURY-INDUCED IMMUNE DEFICIENCY SYNDROME

From Nature Reviews Neuroscience 6, 775-786 (2005); doi:10.1038/nrn1765

Abstract

Infections are a leading cause of morbidity and mortality in patients with acute CNS injury. It has recently become clear that CNS injury significantly increases susceptibility to infection by brain-specific mechanisms: CNS injury induces a disturbance of the normally well balanced interplay between the immune system and the CNS. As a result, CNS injury leads to secondary immunodeficiency — CNS injury-induced immunodepression (CIDS) — and infection. CIDS might serve as a model for the study of the mechanisms and mediators of brain control over immunity. More importantly, understanding CIDS will allow us to work on developing effective therapeutic strategies, with which the outcome after CNS damage by a host of diseases could be improved by eliminating a major determinant of poor recovery.

Summary

1. Infections are a leading cause of death in patients suffering from acute CNS injury, such as stroke, traumatic brain injury or spinal cord injury. In affected patients infections impede neurological recovery and increase morbidity as well as mortality.
2. CNS injury induces a disturbance of the normally well balanced interplay between the immune system and the CNS.
3. Brain injury leads to a characteristic immunological phenotype, which is immunodepressant.
4. During systemic inflammation, either as a result of bacterial infection or injury, the CNS mounts a homeostatic, counter-regulatory anti-inflammatory response. However, when triggered by CNS injury, in the absence of systemic inflammation, this response may be detrimental because it shuts down defence mechanisms, rendering the affected organism susceptible to infection. Under these conditions, the immunodepression exerted by the brain is not balanced by general immunostimulation.
5. CNS injury suppresses cell-mediated immune responses via three major pathways of neuroimmunomodulation: the hypothalamo–pituitary–adrenal (HPA) axis, and the sympathetic and parasympathetic nervous systems.
6. We propose that 'neurogenic' mechanisms are involved in the induction of CNS injury-induced immunodepression (CIDS). Damage to sites in the nervous system that control neural–immune interactions (such as the hypothalamus) may lead to anti-inflammatory signals, without initial involvement of immune mechanisms.
7. CIDS is an important, independent contributor to the negative outcomes of patients with brain injury.
8. Recognizing and understanding CIDS could lead to novel treatment strategies to improve outcome in patients with CNS injury.