Increased vagal tone accounts for the observed immune paralysis in patients with traumatic brain injury

Abstract

Traumatic brain injury (TBI) is a leading cause of death and disability, especially in the younger population. In the acute phase after TBI, patients are more vulnerable to infection, associated with a decreased immune response in vitro. The cause of this immune paralysis is poorly understood. Apart from other neurologic dysfunction, TBI also results in an increase in vagal activity. Recently, the vagus nerve has been demonstrated to exert an anti-inflammatory effect, termed the cholinergic anti-inflammatory pathway. The anti-inflammatory effects of the vagus nerve are mediated by the ␣7 nicotinic acetylcholine receptor present on macrophages and other cytokineproducing cells. From these observations, we hypothesize that the immune paralysis observed in patients with TBI may, at least in part, result from augmented vagal activity and subsequent sustained effects of the cholinergic anti-inflammatory pathway. This pathway may counteract systemic proinflammation caused by the release of endogenous compounds termed alarmins as a result of tissue trauma. However, sustained activity of this pathway may severely impair the body's ability to combat infection. Since the cholinergic anti-inflammatory pathway can be pharmacologically modulated in humans, it could represent a novel approach to prevent infections in patients with TBI. Neurology

The vagal innervation of the gut and immune homeostasis

“…98 Whereas these data suggest that reduced vagal tone increases the setpoint of the immune response with a subtle rise in proinflammatory cytokines and increased disease risk, increased vagal tone resulting from elevated intracranial pressure has been proposed as mechanism underlying the observed immune paralysis in patients with traumatic brain injury. 107 Taken together, these data provide indirect evidence that basal vagal tone may represent an important determinant of the risk to develop or have progression of disease. The finding that exercise or dietary interventions, such as fish oil supplementation to enhance vagal tone may partly explain their beneficial effect on general health.…”

Traumatic Brain Injury: A Disease Process, Not an Event

“…Mirzayan and colleagues (Mirzayan et al, 2008) subjected mice to a controlled cortical impact brain injury and sacrificed them at 96 h. Histopathological changes were found in the liver and lung, suggesting that an isolated TBI can lead to the migration of immune incompetent cells to the peripheral organs, thus potentially leading to their dysfunction. The immune response is significantly impaired acutely following TBI (''post-traumatic immune paralysis''), and may be associated with the high prevalence of infections seen in TBI patients (Kox et al, 2008).…”

The Effects of Brain Injury on Heart Rate Variability and the Innate Immune Response in Critically Ill Patients

“…In our hypothesis, we proposed a critical role for increased intracranial pressure (ICP; Kox et al, 2008). Elevated ICP is a common feature of TBI (Mowery et al, 2008) and SAH (Voldby, 1988).…”

“…The mechanism behind immune paralysis following TBI is poorly understood. We recently hypothesized that the autonomic nervous system, and in particular increased activity of the vagus nerve, may play a role in the observed immune paralysis (Kox et al, 2008). TBI (Baguley et al, 2006;Biswas et al, 2000;Keren et al, 2005) and SAH (Chiu et al, 2011;Kawahara et al, 2003;Svigelj et al, 1996) are associated with autonomic dysfunction, and recent evidence indicates that increased vagus nerve activity can limit the innate immune response (Huston and Tracey, 2011;Tracey, 2002).…”