## 1 Introduction  
The role of the parasympathetic nervous system in modulating the inflammation process has been widely discussed, with a range of evidence supporting the involvement of vagal stimulation on decreasing the amount of pro-inflammatory markers in response to inflammation [1, 2]. The \"cholinergic anti-inflammatory pathway\" is the process by which, in the event of an infection and consequent secretion of pro-inflammatory cytokines in the periphery, the central nervous system (CNS) responds by secreting acetylcholine via different routes, including the vagal route [3, 4, 5, 6]. This acetylcholine interacts with the nicotinic acetylcholine receptor subunit a7 (\(\alpha\)7 nAChR) expressed on the membrane of the innate immune cells to stop the secretion of pro-inflammatory cytokines [7, 8, 9, 10]. As a result, this avoids an over exposure to pro-inflammatory cytokines, as that may damage tissue, impair organ function and could even be lethal [11, 12]. The cholinergic anti-inflammatory pathway has been widely studied. In a study by [PERSON] et al. [13], a group of mice with induced peritoneal sepsis underwent unilateral vagotomy. These authors showed that there was an enhanced host response to infection as, by suppressing the effect of the vagus nerve on the cells of the innate system, there was no release of acetylcholine, which, in turn, did not inhibit the secretion of pro-inflammatory biomarkers. [PERSON] et al. [14] performed a unilateral cervical vagotomy in lipopolysaccharide-charide (LPS)-induced septic rats, and they found that their levels of pro-inflammatory markers were increased because of the vagotomy. Similarly, [PERSON] et al. [15] concluded in their study that the vagotomy was associated with an inhibition of the cholinergic anti-inflammatory pathway, and therefore an over-secretion of pro-inflammatory cytokines. In order to reach these conclusions, they performed a unilateral right cervical vagotomy in a group of mice (\(n=40\)), which had viral myocarditis, and they measured the levels of inflammatory biomarkers IL1, IL6 and TNF\(\alpha\). The results of this group were compared to a group of mice that were subjected to a sham surgery (\(n=40\)) and showed that levels of measured cytokines were significantly higher in the vagotomy group compared to the sham group (\(p<0.05\)). All these studies demonstrate that vagus nerve inhibition enhances the inflammatory response to body injury by increasing the release of inflammatory biomarkers, which can potentially cause effects that are worse than the infection itself [16; 17]. All these studies corroborate the involvement of the autonomic nervous system (ANS) on modulating the initial inflammatory response to infection by means of the cholinergic anti-inflammatory pathway. However, it is worth noting that most of the research found on this topic comes from experimental studies conducted on animal populations under controlled laboratory conditions (such as induced sepsis). This point was also noticed by [PERSON] et al. [18] who agreed that, to their knowledge, there was no clinical study to explore the effect of vagal activity on the immune response to injury and/or pathogens. They therefore used a sample of 183 healthy adults, and they studied the relationship between HRV and the production of lipopolysaccharide-induced inflammatory cytokines and they found out that, as suggested by animal studies, autonomic vagal dysfunction in humans is correlated with an enhanced secretion of pro-inflammatory cytokines (IL1, IL6 and TNF\(\alpha\)) without affecting the secretion of anti-inflammatory cytokines. The study conducted by [PERSON] et al. [18] is pioneering in the human study of vagal activity and its association with the innate immune response. Furthermore, [PERSON] et al. [19] carried out a meta-analysis on HRV and inflammatory markers in humans from 1996 onwards (159 studies), and they found that most research suggested a negative correlation between HRV and inflammatory markers.