R‐flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice
Abstract R‐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 lo...
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| Format: | Article |
| Language: | English |
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Springer Nature
2014-09-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201404168 |
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| author | Katja Schmitz Natasja de Bruin Philipp Bishay Julia Männich Annett Häussler Christine Altmann Nerea Ferreirós Jörn Lötsch Alfred Ultsch Michael J Parnham Gerd Geisslinger Irmgard Tegeder |
| author_facet | Katja Schmitz Natasja de Bruin Philipp Bishay Julia Männich Annett Häussler Christine Altmann Nerea Ferreirós Jörn Lötsch Alfred Ultsch Michael J Parnham Gerd Geisslinger Irmgard Tegeder |
| author_sort | Katja Schmitz |
| collection | DOAJ |
| description | Abstract R‐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. |
| format | Article |
| id | doaj-art-21bfba4003aa438daa7566e0f3f1b1e4 |
| institution | OA Journals |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2014-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-21bfba4003aa438daa7566e0f3f1b1e42025-08-20T02:11:30ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842014-09-016111398142210.15252/emmm.201404168R‐flurbiprofen attenuates experimental autoimmune encephalomyelitis in miceKatja Schmitz0Natasja de Bruin1Philipp Bishay2Julia Männich3Annett Häussler4Christine Altmann5Nerea Ferreirós6Jörn Lötsch7Alfred Ultsch8Michael J Parnham9Gerd Geisslinger10Irmgard Tegeder11Institute of Clinical Pharmacology, Goethe‐University HospitalFraunhofer Institute of Molecular Biology and Applied Ecology, Project Group Translational Medicine and Pharmacology (IME‐TMP)Institute of Clinical Pharmacology, Goethe‐University HospitalInstitute of Clinical Pharmacology, Goethe‐University HospitalInstitute of Clinical Pharmacology, Goethe‐University HospitalInstitute of Clinical Pharmacology, Goethe‐University HospitalInstitute of Clinical Pharmacology, Goethe‐University HospitalInstitute of Clinical Pharmacology, Goethe‐University HospitalDataBionics Research Group, University of MarburgFraunhofer Institute of Molecular Biology and Applied Ecology, Project Group Translational Medicine and Pharmacology (IME‐TMP)Institute of Clinical Pharmacology, Goethe‐University HospitalInstitute of Clinical Pharmacology, Goethe‐University HospitalAbstract R‐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.https://doi.org/10.15252/emmm.201404168endocannabinoidsmultiple sclerosisoptic neuritispainregulatory T cells |
| spellingShingle | Katja Schmitz Natasja de Bruin Philipp Bishay Julia Männich Annett Häussler Christine Altmann Nerea Ferreirós Jörn Lötsch Alfred Ultsch Michael J Parnham Gerd Geisslinger Irmgard Tegeder R‐flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice EMBO Molecular Medicine endocannabinoids multiple sclerosis optic neuritis pain regulatory T cells |
| title | R‐flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice |
| title_full | R‐flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice |
| title_fullStr | R‐flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice |
| title_full_unstemmed | R‐flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice |
| title_short | R‐flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice |
| title_sort | r flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice |
| topic | endocannabinoids multiple sclerosis optic neuritis pain regulatory T cells |
| url | https://doi.org/10.15252/emmm.201404168 |
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