The role of vagus nerve overactivity in the increased incidence of pneumonia following traumatic brain injury.

Nosocomial infections, pneumonia in particular, are well-known complications of traumatic brain injury (TBI), which are associated with a worse neurological outcome. This review aims to explore the role of vagus nerve activity in immunomodulation as a causative factor. A MEDLINE search revealed numerous reports published over the last decade describing the "cholinergic anti-inflammatory pathway" between the vagus nucleus and leukocyte activity. Using a combination of lipopolysaccharide stimulation and vagotomy, it has been shown that the parasympathetic fibres terminating in the spleen reduce tumour necrosis factor production. Further pharmacological and receptor knockout studies have identified the α7 subtype of nicotinic receptors as the likely target for this. Vagal activity also induces changes in neutrophil chemotaxis through altered expression of the CD11b integrin which is abolished by splenectomy. By extrapolating this evidence we suggest a possible mechanism for immunosuppression following TBI which also has the potential to be targeted to reduce the incidence of pneumonia. Whilst there is strong supporting evidence for the role of vagal nerve overactivity in post-TBI pneumonia, there have yet to be any clinical investigations and further study is required.