Recombinant human IL-6 suppresses demyelination in a viral model of multiple sclerosis.
We used a murine model of multiple sclerosis (MS) induced by Theiler's murine encephalomyelitis virus (TMEV) to test the effect of IL-6 on central nervous system (CNS) demyelination. Administration of human rIL-6 (2.5 micrograms/dose), beginning one day before infection and then twice daily for 28 days, dramatically reduced demyelination and inflammation in the spinal cord of susceptible SJL/J mice. Benefit also was observed when rIL-6 was used as a therapeutic agent and begun on day 15 after infection, a time in which there is the first evidence of inflammation and demyelination in the spinal cord. Suppression of myelin damage by treatment with rIL-6 was associated with fewer virus Ag-positive cells in the spinal cord. Infectious CNS virus titers, as measured by plaque assay, were reduced in rIL-6-treated animals on day 15 after infection, but not on day 7, 22, or 29 after infection. Total serum Igs and virus-specific Igs, as detected by indirect ELISA, were increased markedly in rIL-6-treated mice, whereas no effect was observed on TMEV-neutralizing Ab titers. In vivo administration of rIL-6 inhibited a murine CNS-demyelinating disease induced by a virus, suggesting that this IL may have application for the treatment of human MS.
Rodriguez
M
M
Department of Neurology, Mayo Clinic, Rochester, MN 55905.
Pavelko
K D
KD
McKinney
C W
CW
Leibowitz
J L
JL
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D015850:Interleukin-6 / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D011051:Poliomyelitis / Q000276:immunology / Q000473:pathology; D011994:Recombinant Proteins; D013116:Spinal Cord / Q000473:pathology; D017945:Theilovirus / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects
D000956:Antigens, Viral; D015850:Interleukin-6; D011994:Recombinant Proteins