title: Preventive and therapeutic effects of the selective Rho-kinase inhibitor fasudil on experimental autoimmune neuritis.
abstract: We studied the effects of fasudil, a selective Rho-kinase inhibitor, on experimental autoimmune neuritis (EAN). Continuous parenteral administration of fasudil prevented the development of EAN induced by P0 peptide 180-199 in Lewis rats while it also reduced EAN severity when administered after disease onset. Immunohistochemical examination disclosed a marked decrease in the amount of inflammatory cell infiltration and attenuation of demyelination and axonal degeneration. Specific proliferation of lymphocytes from fasudil-treated rats in response to P0 peptide was significantly reduced as compared with those from phosphate-buffered saline (PBS)-treated rats. Fasudil treatment was associated with a significant reduction in secretion of IFN-γ; by contrast, secretion of IL-4 was almost the same in the fasudil- and PBS-treated groups. As a result, the IFN-γ/IL-4 ratio in the supernatant was significantly deceased in fasudil-treated rats compared with PBS-treated ones. Therefore, our results indicate a beneficial effect of selective blockade of Rho-kinase in animals with autoimmune inflammation of the peripheral nerves, and may provide a rationale for the selective blockade of Rho-kinase as a new therapy for Guillain-Barré syndrome.
authors.affiliation: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Arnold Angelo M
authors.initials: AA
authors.lastname: Pineda
authors.forename: Motozumi
authors.initials: M
authors.lastname: Minohara
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Kawamura
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsushita
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamasaki
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Sun
authors.forename: Hua
authors.initials: H
authors.lastname: Piao
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kira
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D018993:Myelin P0 Protein / Q000009:adverse effects; D009444:Neuritis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D020556:Neutrophil Infiltration / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D051381:Rats; D011917:Rats, Inbred Lew; D017923:Sodium-Hydrogen Exchangers; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D018993:Myelin P0 Protein; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil