title: Ribavirin reduces clinical signs and pathological changes of experimental autoimmune encephalomyelitis in Dark Agouti rats.
abstract: The effect of ribavirin on development of experimental autoimmune encephalomyelitis (EAE) was investigated. The disease was induced in genetically susceptible Dark Agouti rats with syngeneic spinal cord homogenate in complete Freund's adjuvant (SCH-CFA). Depending on the amount of mycobacteria in CFA, the animals developed either moderate or severe EAE. Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) was applied i.p. at a daily dosage of 30 mg/kg in two treatment protocols: from the start of immunization (preventive treatment) or from the onset of the first EAE signs after the induction (therapeutic treatment). Signs of EAE began between 7 and 9 days after induction and peaked at days 11-13. In moderate EAE (mean maximal severity score 3.33 +/- 0.21), the recovery was completed by days 23-26, whereas, in severe EAE (mean maximal severity score 4.5 +/- 0.23), obvious recovery was not detected. Preventive ribavirin treatment significantly decreased clinical signs after both moderate (score 1.75 +/- 0.25, P < 0.05) and severe (score 3.62 +/- 0.31, P < 0.015) immunization. Also, disease manifestations were reduced by therapeutic treatment of ribavirin (mean maximal severity score 2.5 +/- 0.2 vs. 3.33 +/- 0.21 in controls, P < 0.005) but less so in comparison with preventive treatment. Analysis of the effects of ribavirin on histopathologic changes in the spinal cord tissue revealed a reduction of mononuclear cell infiltrates, composed of T cells and macrophages/microglia, and the absence of demyelination, which were pronounced in control EAE animals. Beneficial effects of preventive and therapeutic treatment with ribavirin on development of EAE suggest this nucleoside analogue as a useful candidate for therapy in multiple sclerosis.
authors.affiliation: Department of Neurobiology and Immunology, Institute for Biological Research Sinisa Stankovic, University of Belgrade, Belgrade, Yugoslavia.
authors.forename: Irena
authors.initials: I
authors.lastname: Milicevic
authors.forename: Sanja
authors.initials: S
authors.lastname: Pekovic
authors.forename: Sanja
authors.initials: S
authors.lastname: Subasic
authors.forename: Marija
authors.initials: M
authors.lastname: Mostarica-Stojkovic
authors.forename: Stanislava
authors.initials: S
authors.lastname: Stosic-Grujicic
authors.forename: Ljubica
authors.initials: L
authors.lastname: Medic-Mijacevic
authors.forename: Vjera
authors.initials: V
authors.lastname: Pejanovic
authors.forename: Ljubisav
authors.initials: L
authors.lastname: Rakic
authors.forename: Mirjana
authors.initials: M
authors.lastname: Stojiljkovic
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000517:prevention & control; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012254:Ribavirin / Q000494:pharmacology*; D013116:Spinal Cord / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents; D012254:Ribavirin