Down-regulation of experimental allergic encephalomyelitis in DA rats by tiazofurin.
The immunomodulatory potential of tiazofurin (TR) on experimental autoimmune encephalomyelitis (EAE) was investigated. Given continuously, TR dose-dependently suppressed the development of EAE in Dark Agouti (DA) rats immunized with either rat spinal cord homogenate (SCH) or myelin oligodendrocyte glycoprotein (MOG). Amelioration of clinical signs was also obtained when the drug was administered during the inductive phase only (day 0 to 8), or during the effector phase (day 10 to 20) of the disease. Efficacy of TR was further evaluated by adoptive transfer of the disease with myelin basic protein (MBP)-sensitized draining lymph node cells (DLNC). Cells from TR-protected rats failed to transfer the disease into naive syngeneic recipients; in addition, TR treatment of recipient rats that had received MBP-sensitized lymphoid cells diminished the adoptively transferred EAE. A reduction of clinical EAE in TR-treated rats was accompanied with the absence of mononuclear infiltration in the spinal cord and defective adhesive cell-cell interactions. The anti-MOG autoAb production was also decreased. Importantly, no evidence for a generalized impairment of the T cell activity, nor decreased in vitro proliferative antigen specific response of LNC from TR-treated animals was found. These results suggest that TR exerts its EAE protective and suppressive effects by limiting adhesive interactions involved in the autoimmune pathogenic process, and due to the lack of general immunosuppressive activity, it should be considered as a candidate drug for the treatment of neuroinflammatory diseases like multiple sclerosis (MS).
Stosic-Grujicic
Stanislava
S
Institute for Biological Research Sinisa Stankovic, 29 Novembra 142, 11000, Belgrade, Yugoslavia. DUTA@EUnet.yu
Savic-Radojevic
Ana
A
Maksimovic-Ivanic
Danijela
D
Markovic
Milos
M
Bumbasirevic
Vladimir
V
Ramic
Zorica
Z
Mostarica-Stojkovic
Marija
M
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002490:Central Nervous System / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D007107:Immune System / Q000187:drug effects* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009187:Myelitis / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012254:Ribavirin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D007166:Immunosuppressive Agents; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D012254:Ribavirin; C033706:tiazofurin