Can vagus nerve stimulation halt or ameliorate rheumatoid arthritis and lupus?
Acetylcholine, the principal vagus neurotransmitter, inhibits inflammation by suppressing the production of pro-inflammatory cytokines through a mechanism dependent on the α7 nicotinic acetylcholine receptor subunit (alpha7nAChR) that explains why vagus nerve stimulation is anti-inflammatory in nature. Strong expression of alpha7nAChR in the synovium of rheumatoid arthritis and psoriatic arthritis patients was detected. Peripheral macrophages and synovial fibroblasts respond in vitro to specific alpha7nAChR cholinergic stimulation with potent inhibition of proinflammatory cytokines. Fibroblasts balance inflammatory mechanisms and arthritis development through feedback cholinergic stimulation by nearby immune cells. Collagen induced arthritis in alpha7nAChR(-/-) mice was significantly severe and showed increased synovial inflammation and joint destruction compared to the wild-type mice. Similar to vagal nerve stimulation and alpha7nAChR agonists, polyunsaturated fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) also suppress inflammation. In view of their similar anti-inflammatory actions, it is proposed that vagal nerve stimulation, alpha7nAChR agonists and EPA and DHA may augment the formation of anti-inflammatory lipid molecules: lipoxins, resolvins, protectins and maresins. This implies that therapies directed at regulation of the cholinergic and alpha7nAChR mediated mechanisms and enhancing the formation of lipoxins, resolvins, protectins and maresins may halt and/or ameliorate rheumatoid arthritis, lupus and other rheumatological conditions.
UND Life Sciences, 13800 Fairhill Road, #321, Shaker Heights, OH 44120, USA. undurti@hotmail.com
Undurti N
UN
Das
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D002061:Bursa, Synovial / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D018722:Nicotinic Agonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D055536:Vagus Nerve Stimulation; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D005231:Fatty Acids, Unsaturated; D018836:Inflammation Mediators; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000109:Acetylcholine
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