The interface between cholinergic pathways and the immune system and its relevance to arthritis

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arthritis 43 rheumatologydiseases
osteoarthritis 1 rheumatologydiseases
psoriatic arthritis 1 rheumatologydiseases
rheumatoid arthritis 4 rheumatologydiseases
systemic lupus erythematosus 1 rheumatologydiseases

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arthritis 121 Research & TherapyThe interface between cholinergic pathways and the immune system and its relevance to arthritis Robin M McAllenAndrew D CookHsu Wei KhiewDavide MartelliJohn A HamiltonPublication date (epub): 3/2015Publication
arthritis 371 3/2015Publication date (ppub): /2015AbstractThe nervous and immune systems are likely to be interacting in arthritis , with the possible involvement of both neural and non-neural cholinergic transmission. Centrally acting
arthritis 1117 discusses how cholinergic pathways, both neural and non-neural, may impact on inflammation and specifically arthritis . Nicotinic agonists have been reported to reduce the incidence and severity of murine arthritis, albeit
arthritis 1213 specifically arthritis. Nicotinic agonists have been reported to reduce the incidence and severity of murine arthritis , albeit an observation we could not confirm, and clinical studies in rheumatoid arthritis have been
arthritis 1303 of murine arthritis, albeit an observation we could not confirm, and clinical studies in rheumatoid arthritis have been proposed and/or are underway. While the therapeutic potential of nicotinic agonists and vagal
arthritis 1597 pathway’ should not be uncritically embraced as a significant factor in the pathogenesis of rheumatoid arthritis .IntroductionNervous and immune system interactions are likely to be occurring in arthritis, as exemplified
arthritis 1688 rheumatoid arthritis.IntroductionNervous and immune system interactions are likely to be occurring in arthritis , as exemplified by the observation that hemiplegic patients do not develop psoriatic arthritis on their
arthritis 1783 occurring in arthritis, as exemplified by the observation that hemiplegic patients do not develop psoriatic arthritis on their denervated side [[1]]. In this review we will try to identify relevant cholinergic pathways
arthritis 4016 will focus on the control of inflammation and, where specific information exists, its relevance to arthritis . We will then review the pharmacological actions of cholinergic agonists on monocytes/macrophages and
arthritis 4191 agonists on monocytes/macrophages and report new findings on how they affect murine collagen-induced arthritis .Central neural cholinergic pathwaysAround the turn of the century Borovikova and colleagues, working
arthritis 11275 or electrical means. This has implications for its potential role in inflammatory conditions such as arthritis (see below).Where vagotomy does affect inflammationIn contrast to the case with systemic inflammation,
arthritis 15468 but the efferent pathway is sympathetic [[46]].The ‘cholinergic anti-inflammatory pathway’ and arthritis The vagus nerve does not directly innervate the joints, so any action that it may have on arthritis must
arthritis 15567 arthritisThe vagus nerve does not directly innervate the joints, so any action that it may have on arthritis must be indirect. Nevertheless, could a loss of control by the ‘cholinergic anti-inflammatory pathway’
arthritis 15711 could a loss of control by the ‘cholinergic anti-inflammatory pathway’ play a role in maintaining arthritis ? This hypothesis [[47]] was investigated in mice by van Maanen and colleagues [[48]], who found that
arthritis 16042 recently confirmed that unilateral vagotomy had no significant effect. On the other hand, collagen-induced arthritis was found to be exacerbated in mice lacking α7nAChR [[50]], suggesting that nicotinic receptors independent
arthritis 16398 Swedish inpatient register found that surgical vagotomy caused no excess risk of developing rheumatoid arthritis (RA) [[51]], although it did not investigate whether vagotomy affected disease severity.On the other
arthritis 18958 varies inversely with inflammatory markers. Any causative relation remains unproven.Vagal stimulation in arthritis Even if the endogenous role of vagal transmission in the aetiology of arthritis is uncertain, could there
arthritis 19037 unproven.Vagal stimulation in arthritisEven if the endogenous role of vagal transmission in the aetiology of arthritis is uncertain, could there be a therapeutic role for vagal stimulation to relieve arthritis? It is known
arthritis 19128 aetiology of arthritis is uncertain, could there be a therapeutic role for vagal stimulation to relieve arthritis ? It is known that vagal stimulation can suppress limb inflammation (carrageenan-evoked paw oedema) in
arthritis 19450 ‘vagus nerve suspension’, resulted in a modest but significant amelioration of collagen-induced arthritis in rats over 2 to 5 weeks. The authors suggested that the technique caused chronic vagal stimulation,
arthritis 19822 effect of suspension on the vagus might be damage rather than stimulation, or what its mode of action on arthritis might be. Very recently, however, Levine and colleagues [[57]] showed convincingly that electrical stimulation
arthritis 20079 chronically implanted cuff electrodes substantially reduced ankle swelling and histological measures of arthritis in rats with collagen-induced arthritis. The therapeutic effect was well developed within a week of
arthritis 20119 substantially reduced ankle swelling and histological measures of arthritis in rats with collagen-induced arthritis . The therapeutic effect was well developed within a week of stimulation treatment which, strikingly,
arthritis 20656 efferent fibres, visceral afferent fibres or both.Sympathetic preganglionic neurons in inflammation and arthritis The evidence for a role of preganglionic sympathetic neurons (all of which are cholinergic; Figure 1)
arthritis 21377 noradrenergic) is overwhelming. This has been well reviewed elsewhere [[30],[32]].In the context of arthritis , several technical factors prevent us directly inferring the roles of preganglionic sympathetic nerves
arthritis 22415 destroys catecholaminergic immune cells, which play an increasingly dominant role over the time course of arthritis as local noradrenergic terminals withdraw [[59]]; therefore, interpretation of its effects is complicated.
arthritis 22614 effects is complicated. Third, chemical sympathectomy with systemic 6-OHDA in the presymptomatic phase of arthritis lessens disease severity but this treatment during the established phase worsens the disease [[60]],
arthritis 22858 Fourth, local and systemic sympathetic nerves may have opposing actions. In rats given adjuvant-induced arthritis , Lorton and colleagues [[61],[62]] injected 6-OHDA into the lymph nodes that drain the hindlimbs, which
arthritis 23107 including the spleen, but preserved the sympathetic innervation in the limbs. This worsened hindlimb arthritis , even when given presymptomatically. By contrast, systemic 6-OHDA sympathectomised the affected limbs
arthritis 23799 by preganglionic sympathetic neurons [[28],[30]], though this has yet to be tested in the context of arthritis .Non-neural cholinergic pathways, endotoxemia and macrophagesAmong the proinflammatory cytokines, TNF
arthritis 25532 cotinine↓[[69]]NicotineX[[72]]GTS-21↓Nicotine↓[[65]] (mononuclear cells) Whole bloodCholine↓[[64]]NicotineX[[72]]GTS-21↓ (rheumatoid arthritis )Nicotine, GTS-21↓[[71]]Murine Resident peritoneal macrophagesNicotine↓[[13]]Nicotine, AR-R17779↓[[74]]Nicotine↓[[73]]GTS-21↓[[84]] Elicited
arthritis 26584 are obviously some literature data that need to be reconciled.Non-neural cholinergic signalling in arthritis Inflammatory cytokine production in RA whole blood cultures was suppressed by cholinergic agonists [[71]].
arthritis 26971 stimulation in these cells led to potent inhibition of proinflammatory cytokine formation [[79]]. RA and osteo arthritis synovial biopsies had choline acetyltransferase expression in both the fibroblast-like synoviocytes
arthritis 27479 nicotine, and the more specific agonist, AR-R17779, ameliorated and/or delayed murine collagen-induced arthritis [[48],[49]]. In addition, this arthritis in α7nAChR−/− mice was more severe and associated with
arthritis 27520 AR-R17779, ameliorated and/or delayed murine collagen-induced arthritis [[48],[49]]. In addition, this arthritis in α7nAChR−/− mice was more severe and associated with increased proinflammatory cytokine formation
arthritis 27784 knock-out mice have been presented in the same model [[81]]. Nicotine pre-treatment aggravated adjuvant arthritis in rats whereas post-treatment suppressed the disease [[82]]. In our hands, however, both nicotine and
arthritis 27997 AR-R17779, at concentrations similar to those in [[48]], failed to suppress murine collagen-induced arthritis (Figure 2). Such divergent observations again remain to be reconciled. What might help is a thorough
arthritis 28191 help is a thorough analysis of the expression of the different nicotine-binding receptors in various arthritis models.Figure 2Nicotine and AR-R17779 fail to ameliorate collagen-induced arthritis (CIA). Male DBA/1
arthritis 28275 receptors in various arthritis models.Figure 2Nicotine and AR-R17779 fail to ameliorate collagen-induced arthritis (CIA). Male DBA/1 mice (6 to 8 weeks) were immunized for CIA on day 0 (100 μg chick type II collagen
arthritis 29440 treatment with nicotinic agonists has been reported to reduce the incidence and severity of murine arthritis , although we did not confirm this finding. Sympathetic preganglionic neurons also have systemic anti-inflammatory
arthritis 29824 inflammation while the vagal pathway appears not to be. The actions of sympathetic preganglionic neurons on arthritis may be more complex, however, and need to be clarified.It is important that further studies are carried
arthritis 30599 ‘cholinergic ant-inflammatory pathway’ is a significant factor leading to the onset or exacerbation of arthritis [[47]]. The evidence so far indicates that there is no ongoing tone in the vagal ‘cholinergic anti-inflammatory
arthritis 31404 rheumatic diseases’, edited by Rainer Straub. Other articles in this series can be found at http:// arthritis -research.com/series/neurolog
osteoarthritis 26966 stimulation in these cells led to potent inhibition of proinflammatory cytokine formation [[79]]. RA and osteoarthritis synovial biopsies had choline acetyltransferase expression in both the fibroblast-like synoviocytes
psoriatic arthritis 1773 be occurring in arthritis, as exemplified by the observation that hemiplegic patients do not develop psoriatic arthritis on their denervated side [[1]]. In this review we will try to identify relevant cholinergic pathways
rheumatoid arthritis 1292 and severity of murine arthritis, albeit an observation we could not confirm, and clinical studies in rheumatoid arthritis have been proposed and/or are underway. While the therapeutic potential of nicotinic agonists and vagal
rheumatoid arthritis 1586 anti-inflammatory pathway’ should not be uncritically embraced as a significant factor in the pathogenesis of rheumatoid arthritis .IntroductionNervous and immune system interactions are likely to be occurring in arthritis, as exemplified
rheumatoid arthritis 16387 on the Swedish inpatient register found that surgical vagotomy caused no excess risk of developing rheumatoid arthritis (RA) [[51]], although it did not investigate whether vagotomy affected disease severity.On the other
rheumatoid arthritis 25521 cotinine↓[[69]]NicotineX[[72]]GTS-21↓Nicotine↓[[65]] (mononuclear cells) Whole bloodCholine↓[[64]]NicotineX[[72]]GTS-21↓ ( rheumatoid arthritis )Nicotine, GTS-21↓[[71]]Murine Resident peritoneal macrophagesNicotine↓[[13]]Nicotine, AR-R17779↓[[74]]Nicotine↓[[73]]GTS-21↓[[84]] Elicited
systemic lupus erythematosus 17050 balance’, a major determinant of health. Reduced heart rate variability has been described in RA and systemic lupus erythematosus patients [[52]]. In addition, heart rate variability correlated with RA disease severity [[47]] and

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