Limits...
Can vagus nerve stimulation halt or ameliorate rheumatoid arthritis and lupus?

Das UN - Lipids Health Dis (2011)

Bottom Line: 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.Collagen induced arthritis in alpha7nAChR(-/-) mice was significantly severe and showed increased synovial inflammation and joint destruction compared to the wild-type mice.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: UND Life Sciences, 13800 Fairhill Road, #321, Shaker Heights, OH 44120, USA. undurti@hotmail.com

ABSTRACT
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.

Show MeSH

Related in: MedlinePlus

Scheme showing the interaction among VNS, cytokines and PUFAs and their anti-inflammatory metabolites lipoxins, resolvins, protectins and maresins and their role in RA, lupus and IBD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3037330&req=5

Figure 1: Scheme showing the interaction among VNS, cytokines and PUFAs and their anti-inflammatory metabolites lipoxins, resolvins, protectins and maresins and their role in RA, lupus and IBD.

Mentions: It is evident from the preceding discussion that vagus nerve stimulation suppresses inflammation, alpha7nAChR agonists have the ability to ameliorate rheumatoid arthritis, especially in animal models of arthritis whereas arthritis could be exacerbated by vagotomy and suppressed by oral nicotine administration; oral nicotine and/or alpha7nAChR agonists inhibit bone degradation and reduced TNF-α expression in synovial tissue and reduced synovial inflammation (see Figure 1). Thus, vagal tone plays an important role in the pathobiology of inflammation and RA and possibly, other related conditions. Hence, it is proposed that in subjects with RA, lupus and other autoimmune inflammatory diseases the vagal tone is subnormal and sympathetic tone is high. Acetylcholine, the principal vagal neurotransmitter, suppresses inflammation by inhibiting proinflammatory cytokine release through a mechanism that requires alpha7nAChR [6,36-42], while catecholamines have proinflammatory actions [43,44]. Insulin resistance seen in RA, lupus and other autoimmune diseases could also be attributed to reduced vagal tone since, vagus has a regulatory role in insulin secretion and insulin resistance produced by bilateral cervical vagotomy can be reversed by acetylcholine [45-47]. Furthermore, acetylcholine and VNS ameliorate insulin resistance, in part, by enhancing the release of cholecystokinin and incretins [48].


Can vagus nerve stimulation halt or ameliorate rheumatoid arthritis and lupus?

Das UN - Lipids Health Dis (2011)

Scheme showing the interaction among VNS, cytokines and PUFAs and their anti-inflammatory metabolites lipoxins, resolvins, protectins and maresins and their role in RA, lupus and IBD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3037330&req=5

Figure 1: Scheme showing the interaction among VNS, cytokines and PUFAs and their anti-inflammatory metabolites lipoxins, resolvins, protectins and maresins and their role in RA, lupus and IBD.
Mentions: It is evident from the preceding discussion that vagus nerve stimulation suppresses inflammation, alpha7nAChR agonists have the ability to ameliorate rheumatoid arthritis, especially in animal models of arthritis whereas arthritis could be exacerbated by vagotomy and suppressed by oral nicotine administration; oral nicotine and/or alpha7nAChR agonists inhibit bone degradation and reduced TNF-α expression in synovial tissue and reduced synovial inflammation (see Figure 1). Thus, vagal tone plays an important role in the pathobiology of inflammation and RA and possibly, other related conditions. Hence, it is proposed that in subjects with RA, lupus and other autoimmune inflammatory diseases the vagal tone is subnormal and sympathetic tone is high. Acetylcholine, the principal vagal neurotransmitter, suppresses inflammation by inhibiting proinflammatory cytokine release through a mechanism that requires alpha7nAChR [6,36-42], while catecholamines have proinflammatory actions [43,44]. Insulin resistance seen in RA, lupus and other autoimmune diseases could also be attributed to reduced vagal tone since, vagus has a regulatory role in insulin secretion and insulin resistance produced by bilateral cervical vagotomy can be reversed by acetylcholine [45-47]. Furthermore, acetylcholine and VNS ameliorate insulin resistance, in part, by enhancing the release of cholecystokinin and incretins [48].

Bottom Line: 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.Collagen induced arthritis in alpha7nAChR(-/-) mice was significantly severe and showed increased synovial inflammation and joint destruction compared to the wild-type mice.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: UND Life Sciences, 13800 Fairhill Road, #321, Shaker Heights, OH 44120, USA. undurti@hotmail.com

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus