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Centrally acting muscarinic agonists, electrical stimulation of the vagus and treatment with nicotinic receptor agonists can all act systemically to reduce inflammation, although the responsible pathways are incompletely understood. While this \u2018cholinergic anti-inflammatory pathway\u2019 is widely viewed as a significant pathophysiological mechanism controlling inflammation, the evidence supporting this view is critically reviewed and considered inconclusive; an alternative pathway via sympathetic nerves is implicated. This review also 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 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 stimulation is clear, we suggest that the \u2018cholinergic anti-inflammatory pathway\u2019 should not be uncritically embraced as a significant factor in the pathogenesis of rheumatoid arthritis.<\/jats:p>","DOI":"10.1186\/s13075-015-0597-2","type":"journal-article","created":{"date-parts":[[2015,3,30]],"date-time":"2015-03-30T22:01:51Z","timestamp":1427752911000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["The interface between cholinergic pathways and the immune system and its relevance to arthritis"],"prefix":"10.1186","volume":"17","author":[{"given":"Robin M","family":"McAllen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsu Wei","family":"Khiew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Martelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,3,31]]},"reference":[{"key":"597_CR1","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1093\/rheumatology\/32.5.413","volume":"32","author":"D Veale","year":"1993","unstructured":"Veale D, Farrell M, Fitzgerald O. 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