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Because of its anti\u2010inflammatory, endocannabinoid\u2010modulating and antioxidative properties, combined with low toxicity, the present study assessed R\u2010flurbiprofen in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis in mice. Oral R\u2010flurbiprofen prevented and attenuated primary progressive EAE in C57BL6\/J mice and relapsing\u2010remitting EAE in SJL mice, even if the treatment was initiated on or after the first flare of the disease. R\u2010flurbiprofen reduced immune cell infiltration and microglia activation and inflammation in the spinal cord, brain and optic nerve and attenuated myelin destruction and EAE\u2010evoked hyperalgesia. R\u2010flurbiprofen treatment increased CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    FoxP3\n                    <jats:sup>+<\/jats:sup>\n                    regulatory T cells, CTLA4\n                    <jats:sup>+<\/jats:sup>\n                    inhibitory T cells and interleukin\u201010, whereas the EAE\u2010evoked upregulation of pro\u2010inflammatory genes in the spinal cord was strongly reduced. The effects were associated with an increase of plasma and cortical endocannabinoids but decreased spinal prostaglandins, the latter likely due to R to S inversion. The promising results suggest potential efficacy of R\u2010flurbiprofen in human MS, and its low toxicity may justify a clinical trial.\n                  <\/jats:p>","DOI":"10.15252\/emmm.201404168","type":"journal-article","created":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T04:05:30Z","timestamp":1412136330000},"page":"1398-1422","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["R\u2010flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice"],"prefix":"10.1038","volume":"6","author":[{"given":"Katja","family":"Schmitz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasja","family":"de Bruin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Bishay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"M\u00e4nnich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annett","family":"H\u00e4ussler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Altmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerea","family":"Ferreir\u00f3s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rn","family":"L\u00f6tsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Ultsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Parnham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Geisslinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irmgard","family":"Tegeder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,9,30]]},"reference":[{"key":"BFEMMM201404168_CR1","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/nn1916","volume":"10","author":"N Agarwal","year":"2007","unstructured":"Agarwal N, Pacher P, Tegeder I, Amaya F, Constantin CE, Brenner GJ, Rubino T, Michalski CW, Marsicano G, Monory K, et\u00a0al (2007) Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors. 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