The Involvement of Parasympathetic and Sympathetic Nerve in the Inflammatory Reflex

Abstract

Production of inflammatory cytokines plays important roles in the response against tissue injury and in host defense. Alterations in the production of inflammatory cytokines may cause local or systemic inflammatory imbalance, culminating in organ failure or lethal systemic inflammation. The cholinergic anti-inflammatory pathway has been implicated as an important mechanism to regulate inflammation of targeted tissue. In this review, we discuss important advances, conflicting and controversial findings regarding the involvement of parasympathetic vagus and sympathetic splenic nerve through acetylcholine (ACh) release and α7 nicotinic acetylcholine receptor (nAChRα7) activation in the spleen. In addition, we address the involvement of cholinergic control of inflammation in other organs innerved by the vagus nerve such as gut, liver, kidney and lung, and independent of parasympathetic innervations such as skin and skeletal muscle. Then, other structures and mechanisms independent of vagus or splenic nerve may be involved in this process, such as local cells and motor neurons producing ACh. Altogether, the convergence of these findings may contribute to current anti-inflammatory strategies involving selective drug-targeting and electrical nerve stimulation. J. Cell. Physiol. 231: 1862-1869, 2016. © 2016 Wiley Periodicals, Inc.

Hypothalamic AMP-Activated Protein Kinase Regulates Biphasic Insulin Secretion from Pancreatic β Cells during Fasting and in Type 2 Diabetes

“…The effects of PNx might result from reduced glucose toxicity (Rossetti et al, 1990). Furthermore, PNx might affect β cell death directly by modulating intracellular metabolism or by inhibiting islet inflammation via sympathetic immune modulation (Pereira and Leite, 2016). Although the mechanism remains unclear, our results suggest a concept for future diabetic therapy and indicate the need for further study of the mechanisms that control both the quality and quantity of insulin secretion.…”

Cholinergic modulation of the immune system presents new approaches for treating inflammation

“…Based on these findings, Tracey and colleagues coined the term “cholinergic anti-inflammatory pathway” (Borovikova et al, 2000). Over the intervening years, many studies have built on this initial description of the cholinergic anti-inflammatory pathway to yield our current view, which casts the spleen as the major effector (Andersson and Tracey, 2012; Bonaz et al, 2016b; Pavlov and Tracey, 2015; Pereira and Leite, 2016).…”

“…However, these findings do not provide an explanation for the wealth of experimental data showing anti-inflammatory responses to selective stimulation of vagal efferent nerve fibers. This controversy is addressed in several recent reviews (Bonaz et al, 2016b; Martelli et al, 2014a; Pereira and Leite, 2016).…”

Skeletal muscle inflammation and atrophy in heart failure

“…Lastly, increased local and systemic sympathetic nerve activity and reduce vagal tone have important effects on innate immune cell recruitment, pro-inflammatory signaling, and resolution of inflammatory responses. Sympathetic activation is an essential cue to mobilize monocytes from the bone marrow potentially through a β3-adrenergic mechanism, while parasympathetic signaling via nicotinic acetylcholine receptors is an important negative regulator of pro-inflammatory innate immune responses to sterile tissue injury[16;26;71]. …”