Figure 2
Wiring of the cholinergic antiinflammatory pathway, which balances cytokine production.
Pathogens as well as ischemia and other forms of injury activate cytokine production, which normally restores health. If the cytokine response is unbalanced or excessive, however, then these same mediators can cause disease. Efferent signals from the vagus nerve, which can be controlled by brain networks, inhibit cytokine production via pathways dependent on the α7 subunit of the AChR on macrophages and other cells. Efferent vagus nerve activity also increases instantaneous heart rate variability. A cholinergic brain network that is responsive to M1 agonists can increase the activity of the cholinergic antiinflammatory pathway and also increase instantaneous heart rate variability. Afferent signals carried in the vagus nerve can activate an efferent response that inhibits cytokine release, termed the inflammatory reflex.
