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In one circuit, termed \u201cthe inflammatory reflex,\u201d action potentials transmitted in the vagus nerve inhibit the production of tumor necrosis factor (TNF), an inflammatory molecule that is a major therapeutic target in RA. Although studied in animal models of arthritis and other inflammatory diseases, whether electrical stimulation of the vagus nerve can inhibit TNF production in humans has remained unknown. The positive mechanistic results reported here extend the preclinical data to the clinic and reveal that vagus nerve stimulation inhibits TNF and attenuates disease severity in RA patients.<\/jats:p>","DOI":"10.1073\/pnas.1605635113","type":"journal-article","created":{"date-parts":[[2016,7,5]],"date-time":"2016-07-05T22:50:23Z","timestamp":1467759023000},"page":"8284-8289","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":981,"title":["Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis"],"prefix":"10.1073","volume":"113","author":[{"given":"Frieda A.","family":"Koopman","sequence":"first","affiliation":[{"name":"Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeeta S.","family":"Chavan","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Science, Feinstein Institute for Medical Research, Manhasset, NY 11030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanda","family":"Miljko","sequence":"additional","affiliation":[{"name":"University Clinical Hospital, Mostar 88000, Bosnia and Herzegovina;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simeon","family":"Grazio","sequence":"additional","affiliation":[{"name":"Clinical Hospital Center Sestre Milosrdnice, Zagreb 10000, Croatia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sekib","family":"Sokolovic","sequence":"additional","affiliation":[{"name":"Sarajevo University Clinical Center, Sarajevo 71000, Bosnia and Herzegovina;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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