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EMBO Mol Med. 2014 Nov;6(11):1398-422. doi: 10.15252/emmm.201404168.

R-flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice.

Author information

1
Institute of Clinical Pharmacology Goethe-University Hospital, Frankfurt am Main, Germany.
2
Fraunhofer Institute of Molecular Biology and Applied Ecology Project Group Translational Medicine and Pharmacology (IME-TMP), Frankfurt am Main, Germany.
3
Institute of Clinical Pharmacology Goethe-University Hospital, Frankfurt am Main, Germany Fraunhofer Institute of Molecular Biology and Applied Ecology Project Group Translational Medicine and Pharmacology (IME-TMP), Frankfurt am Main, Germany.
4
DataBionics Research Group, University of Marburg, Marburg, Germany.
5
Institute of Clinical Pharmacology Goethe-University Hospital, Frankfurt am Main, Germany Fraunhofer Institute of Molecular Biology and Applied Ecology Project Group Translational Medicine and Pharmacology (IME-TMP), Frankfurt am Main, Germany tegeder@em.uni-frankfurt.de.

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.

KEYWORDS:

endocannabinoids; multiple sclerosis; optic neuritis; pain; regulatory T cells

PMID:
25269445
PMCID:
PMC4237468
DOI:
10.15252/emmm.201404168
[Indexed for MEDLINE]
Free PMC Article

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