Ribavirin ameliorates experimental autoimmune encephalomyelitis in rats and modulates cytokine production.
To determine the mechanism underlying ribavirin induced amelioration of experimental autoimmune encephalomyelitis (EAE), cytokine profiles were evaluated in draining lymph node (DLN) cell culture supernatants and spinal cord obtained from EAE and/or ribavirin-treated EAE Dark Agouti rats. Administration of ribavirin to EAE rats markedly affected the production of pro-inflammatory cytokines IFN-gamma, IL-1beta and TNF-alpha in DLN and spinal cord, thus shifting the balance towards the anti-inflammatory cytokines IL-10 and TGF-beta. These findings suggest that ribavirin attenuates EAE by limiting cytokine-mediated immunoinflammatory events leading to CNS destruction. The conducted experiments provide rationale for ribavirin to be considered as a candidate drug in the development of new therapeutic strategies for the treatment of autoimmune diseases in humans, such as multiple sclerosis.
Lavrnja
Irena
I
Department of Neurobiology, Institute for Biological Research Sinisa Stankovic, University of Belgrade, Serbia. irenam@ibiss.bg.ac.yu
Stojkov
Danijela
D
Bjelobaba
Ivana
I
Pekovic
Sanja
S
Dacic
Sanja
S
Nedeljkovic
Nadezda
N
Mostarica-Stojkovic
Marija
M
Stosic-Grujicic
Stanislava
S
Rakic
Ljubisav
L
Stojiljkovic
Mirjana
M
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology; D051381:Rats; D012254:Ribavirin / Q000627:therapeutic use*; D013116:Spinal Cord / Q000473:pathology
D000998:Antiviral Agents; D016207:Cytokines; D012254:Ribavirin