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R-flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice

 
: Schmitz, K.; Bruin, N. de; Bishay, P.; Männich, J.; Häussler, A.; Altmann, C.; Ferreirós, N.; Lötsch, J.; Ultsch, A.; Parnham, M.J.; Geisslinger, G.; Tegeder, I.

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Postprint (7.5 MByte; PDF; )

EMBO molecular medicine 6 (2014), No.11, pp.1398-1422
ISSN: 1757-4676
ISSN: 1757-4684
English
Journal Article, Electronic Publication
Fraunhofer IME ()

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.

: http://publica.fraunhofer.de/documents/N-319605.html