Chronic allostatic load, a burden of chronic stress and accompanying changes in personal behaviors, may lead to a disease in the long-run, mediated via autonomic, neuroendocrine, or immune system activity (McEwen 1998). Sympathetic predominance, vagal withdrawal, and baroreflex impairment represent the autonomic counterpart of the complex psychophysiological changes underlying the increase in cardiovascular risk associated with long-lasting stress (Rosengren et al. 2004). As previously noted, chronic psychological stress and the inflammatory response have been implicated in the etiology and pathogenesis of certain cardiovascular diseases, such as atherosclerosis, and of other diseases, e.g., obesity (Hamer et al. 2012). However, the response of vagal-immune pathway to allostatic load evoked by chronic stress is still unclear. In acute stress, Weber et al. (2010) demonstrated that healthy subjects with low HRV had delayed recovery of TNF-α up to an hour after the stressor had ended and suggest that vagal function is coordinated with the regulation of both acute as well as chronic inflammation in healthy humans. Our results support this hypothesis. Decreased cardiovagal regulation associated with a greater immune response as a result of allostatic load evoked by a long-lasting stress-related exam period could represent the pathomechanism by which dysregulated vagal-immune homeostasis increases the risk of inflammatory conditions associated with chronic real-life stress.

Several explanations are assumed for these findings. Firstly, the common central neural areas regulating both immune and cardiovagal functions were found in recent studies. For example, the neuroimaging research showed associations between vagally mediated HRV and activity in specific brain areas, such as prefrontal, anterior cingulate cortex, insula, or amygdala (Thayer et al. 2012). These brain areas are also associated with the regulation of immune responses (Rosenkranz et al. 2005). Thus, cortical structures are involved in immunomodulation at least partially via the neural concomitants of the cholinergic anti-inflammatory pathway (Thayer et al. 2011). Taken together, the altered vagal-immune communication can be explained by discrete stress-linked control abnormalities in the common neurobiological regulatory basis for both autonomic and immune systems. Furthermore, the neurovisceral theory emphasizes the tonic inhibitory control of the prefrontal cortex on the subcortical regions, including amygdala, linked to the regulation of the immune system via the vagus nerve (Thayer and Sternberg 2006). Consequently, lack of inhibitory input by the vagus nerve might lead to perturbations in the neuroimmune pathway involved with the allostatic overload as observed in our studied group.