Intrathecal administration of neutralizing antibody against Fas ligand suppresses the progression of experimental autoimmune encephalomyelitis.
A therapy aimed at blocking the Fas/Fas ligand (FasL) system was investigated using a relapsing form of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of multiple sclerosis (MS). Intracisternal administration of neutralizing antibody against FasL during the progression phase of EAE significantly reduced the severity of the disease with milder inflammation and myelin breakdown in the central nervous system (CNS). These results raised the possibility that the Fas/FasL system might contribute to tissue destruction in the CNS in the acute phase of EAE and that the intrathecal administration of neutralizing antibody against FasL may be beneficial for suppression of the acute phase of MS.
Okuda
Y
Y
Neuroimmunology Laboratory, La Trobe University, Bundoora, Victoria, 3083, Australia. yoshiok@bioserve.latrobe.edu.au
Sakoda
S
S
Fujimura
H
H
Nagata
S
S
Yanagihara
T
T
Bernard
C C
CC
D000208:Acute Disease; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D053222:Fas Ligand Protein; D005260:Female; D006651:Histocytochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000276:immunology; D007278:Injections, Spinal; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D004676:Myelin Basic Protein / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein