The Vagus Nerve and Nicotinic Receptors Involve Inhibition of HMGB1 Release and Early Pro-inflammatory Cytokines Function in Collagen-Induced Arthritis

Abstract

The cholinergic anti-inflammatory pathway has an anti-inflammatory role in the pathophysiology of rheumatoid arthritis (RA) via inhibiting HMGB1 release and early pro-inflammatory cytokines function. Study of this pathway could be used for RA therapy.

Presence of ChAT mRNA and a very marked α7nAChR immunoreaction in the synovial lining layer of the knee joint

“…Vagotomy thus exacerbates arthritis in mice, whereas oral nicotine administration or nicotine injections ameliorate the arthritic process (van Maanen et al, 2009;Li et al, 2010). Electrical stimulation of the vagus nerve in vivo during lethal endotoxaemia is shown to lead to an inhibition of TNF-alpha synthesis in the liver, and an attenuation of peak serum TNF-alpha levels (Borovikova et al, 2000).…”

Restoring the Balance of the Autonomic Nervous System as an Innovative Approach to the Treatment of Rheumatoid Arthritis

“…Receptor activation by specific agonists effectively attenuated immune responses and ameliorated disease severity in different experimental settings, including animal models for sepsis (73,74), pancreatitis (75), ischemia-reperfusion injury (76), postoperative ileus (77), acute lung injury (73), and, as discussed in more detail below, CIA (78,79). Moreover, in α7-subunit-deficient mice, VNS failed to reduce serum TNF-α levels during endotoxemia (64).…”

“…The cholinergic antiinflammatory pathway can be stimulated by pharmacologic activation of the nAChRs. The observation that specific nAChRα7 agonists diminish disease in several animal models of inflammation, including animal models for arthritis (78,79) and experimental colitis (98), suggests that therapeutic agents that can modify cholinergic signaling might be beneficial in humans. Nicotine, a potent nAChRα7 agonist, has been used extensively to examine the cholinergic antiinflammatory pathway in animal models.…”

Ultrasonic Stimulation of the Cholinergic Anti-Inflammatory Pathway for Renal Protection

“…At the cellular level, a7nAchR activation suppresses NFkB translocation into the nucleus and the subsequent release of pro-inflammatory molecules (e.g., TNF-a, IL-1b, IL-6, IL-18, and high-mobility group box-1 [HMGB1]). 6 The Jak2-Stat3 signaling pathway operates downstream of the a7nAchR, and IL-10 release seems unaffected. 7 In addition to DAMPs and PAMPs, inflammatory cytokines (e.g., IL-1b) also stimulate the vagus afferent nerve endings.…”

“…7 In addition to DAMPs and PAMPs, inflammatory cytokines (e.g., IL-1b) also stimulate the vagus afferent nerve endings. 6 Importantly, this inflammatory reflex is a key factor in the maintenance of immunologic homeostasis, preventing nonresolving inflammation after a variety of insults. Clearly, the cholinergic anti-inflammatory pathway depends on the expression of the a7nAchR.…”