The selective Rho-kinase inhibitor Fasudil is protective and therapeutic in experimental autoimmune encephalomyelitis

  • J Neuroimmunol. 2006 Nov;180(1-2):126-34. doi: 10.1016/j.jneuroim.2006.06.027.
Xiaojia Sun  1 ,  Motozumi Minohara ,  Hitoshi Kikuchi ,  Takaaki Ishizu ,  Masahito Tanaka ,  Hua Piao ,  Manabu Osoegawa ,  Yasumasa Ohyagi ,  Hiroaki Shimokawa ,  Jun-Ichi Kira
Affiliations
  • 1. Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
PMID: 16996142 DOI: 10.1016/j.jneuroim.2006.06.027
Abstract

We studied the role of fasudil, a selective Rho-kinase inhibitor, in experimental autoimmune encephalomyelitis (EAE). Both parenteral and oral administration of fasudil prevented the development of EAE induced by proteolipid protein (PLP) p139-151 in SJL/J mice. Specific proliferation of lymphocytes to PLP was significantly reduced, together with a downregulation of interleukin (IL)-17 and a marked decrease of the IFN-gamma/IL-4 ratio. Immunohistochemical examination also disclosed a marked decrease of inflammatory cell infiltration, and attenuated demyelination and acute axonal transaction. These results may provide a rationale of selective blockade of Rho-kinase by oral use of fasudil as a new therapy for multiple sclerosis.

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