Schmitz, K.K.SchmitzBruin, N. deN. deBruinBishay, P.P.BishayMännich, J.J.MännichHäussler, A.A.HäusslerAltmann, C.C.AltmannFerreirós, N.N.FerreirósLötsch, J.J.LötschUltsch, A.A.UltschParnham, M.J.M.J.ParnhamGeisslinger, G.G.GeisslingerTegeder, I.I.Tegeder2022-03-042022-03-042014https://publica.fraunhofer.de/handle/publica/23785310.15252/emmm.2014041682-s2.0-84911396402R-flurbiprofen is the non-cyclooxygenase inhibiting R-enantiomer of the non-steroidal anti-inflammatory drug flurbiprofen, which was assessed as a remedy for Alzheimer's disease. Because of its anti-inflammatory, endocannabinoid-modulating and antioxidative properties, combined with low toxicity, the present study assessed R-flurbiprofen in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis in mice. Oral R-flurbiprofen prevented and attenuated primary progressive EAE in C57BL6/J mice and relapsing-remitting EAE in SJL mice, even if the treatment was initiated on or after the first flare of the disease. R-flurbiprofen reduced immune cell infiltration and microglia activation and inflammation in the spinal cord, brain and optic nerve and attenuated myelin destruction and EAE-evoked hyperalgesia. R-flurbiprofen treatment increased CD4(+)CD25(+)FoxP3(+) regulatory T cells, CTLA4(+) inhibitory T cells and interleukin-10, whereas the EAE-evoked upregulation of pro-inflammatory 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-flurbiprofen in human MS, and its low toxicity may justify a clinical trial.enjournal article