Abstract
A recent study in rheumatoid arthritis (RA) patients using electrical vagus nerve stimulation (VNS) to activate the inflammatory reflex has shown promising effects on disease activity. Innervation by the autonomic nerve system might be involved in the regulation of many endocrine and metabolic processes and could therefore theoretically lead to unwanted side effects. Possible effects of VNS on secretion of hormones are currently unknown. Therefore, we evaluated the effects of a single VNS on plasma levels of pituitary hormones and parameters of postprandial metabolism. Six female patients with RA were studied twice in balanced assignment (crossover design) to either VNS or no stimulation. The patients selected for this substudy had been on VNS therapy daily for at least 3 months and at maximum of 24 months. We compared 10-, 20-, and 30-min poststimulus levels to baseline levels, and a 4-h mixed meal test was performed 30 min after VNS. We also determined energy expenditure (EE) by indirect calorimetry before and after VNS. VNS did not affect pituitary hormones (growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, prolactin, follicle-stimulating hormone, and luteinizing hormone), postprandial metabolism, or EE. Of note, VNS reduced early postprandial insulin secretion, but not AUC of postprandial plasma insulin levels. Cortisol and catecholamine levels in serum did not change significantly. Short stimulation of vagal activity by VNS reduces early postprandial insulin secretion, but not other hormone levels and postprandial response. This suggests VNS as a safe treatment for RA patients.
Highlights
The autonomous nervous system and the immune system interact in both directions via neurotransmitters, cytokines, and hormones [1, 2]
It has been shown that free fatty acids, norepinephrine, and pancreatic polypeptide levels are increased in individuals at risk for development of rheumatoid arthritis (RA) and RA patients, compared to healthy individuals [9]
Insulin, Free fatty acids (FFAs), Insulin-like growth factor-1 (IGF-1), and bile acid levels were comparable on study days and were not changed by vagus nerve stimulation (VNS) alone (Fig. 3)
Summary
The autonomous nervous system and the immune system interact in both directions via neurotransmitters, cytokines, and hormones [1, 2]. Recent prospective observational studies indicate that impaired constitutive vagus nerve activity precedes the development of clinically manifest rheumatoid arthritis (RA) [6] Activation of this pathway through electrical vagus nerve stimulation (VNS) could be a feasible and effective treatment in reducing pathological systemic inflammation in RA and other inflammatory diseases like Crohn’s disease [7, 8]. The left vagus nerve was isolated within the sheath between the carotid artery and the internal jugular vein and a VNS lead with three helical coiled cuffs was placed around the vagus nerve With this approach, we cannot exclude the possibility that VNS has effects in other vagal targets, such as the pituitary gland and the central nervous system
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