Autonomic Nervous System and Immune System Interactions

Abstract

The present review assesses the current state of literature defining integrative autonomic-immune physiological processing, focusing on studies that have employed electrophysiological, pharmacological, molecular biological and central nervous system experimental approaches. Central autonomic neural networks are informed of peripheral immune status via numerous communicating pathways, including neural and non-neural. Cytokines and other immune factors affect the level of activity and responsivity of discharges in sympathetic and parasympathetic nerves innervating diverse targets. Multiple levels of the neuraxis contribute to cytokine-induced changes in efferent parasympathetic and sympathetic nerve outflows, leading to modulation of peripheral immune responses. The functionality of local sympathoimmune interactions depends on the microenvironment created by diverse signaling mechanisms involving integration between sympathetic nervous system neurotransmitters and neuromodulators; specific adrenergic receptors; and the presence or absence of immune cells, cytokines and bacteria. Functional mechanisms contributing to the cholinergic anti-inflammatory pathway likely involve novel cholinergic-adrenergic interactions at peripheral sites, including autonomic ganglion and lymphoid targets. Immune cells express adrenergic and nicotinic receptors. Neurotransmitters released by sympathetic and parasympathetic nerve endings bind to their respective receptors located on the surface of immune cells and initiate immune-modulatory responses. Both sympathetic and parasympathetic arms of the autonomic nervous system are instrumental in orchestrating neuroimmune processes, although additional studies are required to understand dynamic and complex adrenergic-cholinergic interactions. Further understanding of regulatory mechanisms linking the sympathetic nervous, parasympathetic nervous, and immune systems is critical for understanding relationships between chronic disease development and immune-associated changes in autonomic nervous system function.

Effect of ghrelin on regulation of splenic sympathetic nerve discharge

“…However, recent lines of inquiry have established a role for the SNS in mediating neural-immune interactions (Kenney et al, 2014). Moreover, it is well-established that ghrelin can exert potent anti-inflammatory effects both in vitro and in vivo, with a promising therapeutic outlook in the treatment of inflammatory diseases (Vanessa et al, 2013).…”

“…Numerous bidirectional pathways provide the foundation for communication between the nervous system and the immune system, and the efferent arm of the SNS plays an important role in mediating neural-immune interactions (Kenney et al, 2014). Physiological activation of splenic SND enhances the expression of splenic cytokine and chemokine genes, an effect that is abrogated by splenic nerve denervation (Ganta et al, 2004), indicating that changes in the level of efferent splenic nerve outflow can influence immune function in a peripheral lymphoid organ.…”

Toll-like receptor-4 signaling pathway in aorta aging and diseases: “its double nature”

“…This regulation (similarly to that regulating the entire cardiovascular system) is dominated by the central nervous system (CNS) [151], the knowledge of which in the past 20 years has significantly evolved. This control is also supported, or rather induced by autonomic nervous system (ANS) [152], which completes the primary ring of homeostasis body's control along with the immune and endocrine systems. These latter, through molecular pathways of innate signaling (likely TLR-4 signaling pathway) and hormones (i.e.…”

“…These latter, through molecular pathways of innate signaling (likely TLR-4 signaling pathway) and hormones (i.e. reproductive hormones), which were not classically viewed as CV (aorta included) signaling pathways, mediate both ANS and CNS target effects in traditional and not traditional manner [152]. In fact, they also act via membrane receptor-independent signaling mechanisms and ROS, all of which have been shown to have profound effects on the central control of blood pressure and activity of stress and stretch signaling pathways of aortic EC and VSCM cells [153,154].…”

In vivo detection of clinically non-apparent ocular surface inflammation in patients with meibomian gland dysfunction-associated refractory dry eye symptoms: a pilot study

“…Some of these sensory neuropeptide receptors are also found on the neurovascular complex associated with meibomian gland acini, 45,47 allowing circulating neuropeptides and cytokines to indirectly regulate both sensory stimuli and meibomian gland function. Given the propensity for autonomic-immune interactions following cytokine release by immune cells, 48 it seems plausible that the presence of immune cells in the vicinity of palpebral conjunctival epithelium, substantia propria, and meibomian glands, as seen on IVCM, may stimulate these sensory nerves to trigger sensations of eye dryness and discomfort as reported by the patients presented in this paper. 44,45,49 Thus, a completely accurate assessment of the health of the ocular surface, at least in some patients, may not be made based on slit-lamp examination alone given the microanatomy of the meibomian gland and associated architectural changes in disease, 50,51 which could have therapeutic implications in these patients.…”