Intrathecal administration of antibodies against LFA-1 and against ICAM-1 suppresses experimental allergic encephalomyelitis in rats.
The effects of intracerebroventricular administration of mAbs against LFA-1 and ICAM-1 on both active and passive experimental allergic encephalomyelitis (EAE) in rats were examined. Lewis rats were immunized with guinea pig myelin basic protein (MBP) or MBP 68-86 peptide in complete Freund's adjuvant to induce active EAE, or they were injected with encephalitogenic MBP-reactive lymphocytes for adoptive transferred EAE. LFA-1-specific mAbs and/or ICAM-1-specific mAbs or a control mAb or PBS were injected into the lateral ventricles via implanted needles. Intracerebroventricular administration of the specific mAbs together on Days 0, 2, 4, and 6 or on Days 4, 6, 8, and 10 after immunization almost completely suppressed the clinical signs of the actively induced EAE with reduced numbers of the infiltrating cells and reduced percentages of W3/25(+) and IA-29(+) cells in the central nervous system (CNS) of the rats. Pretreatment with both specific mAbs from 14 to 11 days prior to immunization also exhibited a considerable protective effect. However, daily injection from Day 10 to 13 after immunization did not suppress the clinical signs. In rats with adoptive transferred EAE, daily treatment from Day 0 to Day 4 after cell transfer completely abolished clinical signs of EAE, although comparison of histological findings was not remarkable. In conclusion, intrathecal administration of antibodies against LFA-1 and ICAM-1 may be useful for the treatment of human demyelinating diseases, such as multiple sclerosis.
Kawai
K
K
Department of Neurology, Nagoya University School of Medicine, Japan.
Kobayashi
Y
Y
Shiratori
M
M
Sobue
G
G
Tamatani
T
T
Miyasaka
M
M
Yoshikai
Y
Y
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D002478:Cells, Cultured; D002552:Cerebral Ventricles; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology*; D006168:Guinea Pigs; D006801:Humans; D007116:Immunization, Passive; D007124:Immunoenzyme Techniques; D007278:Injections, Spinal; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D011917:Rats, Inbred Lew
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1