Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin

Abstract

Vertebrates achieve internal homeostasis during infection or injury by balancing the activities of proinflammatory and anti-inflammatory pathways. Endotoxin (lipopolysaccharide), produced by all gram-negative bacteria, activates macrophages to release cytokines that are potentially lethal. The central nervous system regulates systemic inflammatory responses to endotoxin through humoral mechanisms. Activation of afferent vagus nerve fibres by endotoxin or cytokines stimulates hypothalamic-pituitary-adrenal anti-inflammatory responses. However, comparatively little is known about the role of efferent vagus nerve signalling in modulating inflammation. Here, we describe a previously unrecognized, parasympathetic anti-inflammatory pathway by which the brain modulates systemic inflammatory responses to endotoxin. Acetylcholine, the principle vagal neurotransmitter, significantly attenuated the release of cytokines (tumour necrosis factor (TNF), interleukin (IL)-1beta, IL-6 and IL-18), but not the anti-inflammatory cytokine IL-10, in lipopolysaccharide-stimulated human macrophage cultures. Direct electrical stimulation of the peripheral vagus nerve in vivo during lethal endotoxaemia in rats inhibited TNF synthesis in liver, attenuated peak serum TNF amounts, and prevented the development of shock.

Alteration of Cholinergic Anti‐Inflammatory Pathway in Rat With Ischemic Cardiomyopathy–Modified Electrophysiological Function of Heart

“…In contrast, our study suggested that unilateral vagotomy not only aggravated the abnormality of ICM rats and increased the inducibility quotient of ventricular arrhythmias but also attenuated the effects of eliciting CAP. It was also reported that vagotomy attenuated the anti‐inflammatory effect of CAP and thereby enhanced cytokine release in response to LPS treatment 41, 42. Thus, vagotomy, performed in an ICM rat, increased the release of cytokines and collagens and altered the sympathetic/parasympathetic ratio, which served as a harmful role of ventricular arrhythmia.…”

Effect of exercise on cardiac autonomic function in females with rheumatoid arthritis

“…Conventional risk factors (abnormal body mass index (BMI), abnormal lipogram, smoking, hypertension, diabetes mellitus, family history of cardiac disease and a personal history of cardiac disease) [8,9], accelerated atherosclerosis due to inflammation [7,10,11], and autonomic dysfunction [12][13][14][15] can all play a role in the etiopathogenesis.…”

The α7 nicotinic acetylcholine receptor on fibroblast‐like synoviocytes and in synovial tissue from rheumatoid arthritis patients: A possible role for a key neurotransmitter in synovial inflammation

“…In recent years, it has been demonstrated that the cholinergic nervous system can regulate inflammation via its principal neurotransmitter, ACh, a concept referred to as the "cholinergic antiinflammatory pathway" (5). ACh can interact with members of the nAChR family.…”

“…The ␣7nAChR is expressed by various immune cells, including monocytes (15), macrophages (5,16), T and B lymphocytes (17,18), and dendritic cells (19). In addition to this classic ␣7nAChR, the human genome contains an alternative ␣7 transcript designated dup␣7 or "cholinergic receptor family with sequence similarity to 7A" (CHRFAM7A) (20).…”