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 ence phalomyelitis (EAE) in rats were examined. Lewis rats were immunized w ith guinea pig myelin basic protein (MBP) or MBP 68-86 peptide in comp lete Freund's adjuvant to induce active EAE, or they were injected wit h encephalitogenic MBP-reactive lymphocytes for adoptive transferred E AE. LFA-1-specific mAbs and/or ICAM-1-specific mAbs or a control mAb o r 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 a lmost completely suppressed the clinical signs of the actively induced EAE with reduced numbers of the infiltrating cells and reduced percen tages of W3/25(+) and 1A-29(+) cells in the central nervous system (CN S) of the rats. Pretreatment with both specific mAbs from 14 to 11 day s prior to immunization also exhibited a considerable protective effec t. However, daily injection from Day 10 to 13 after immunization did n ot suppress the clinical signs. In rats with adoptive transferred EAE, daily treatment from Day 0 to Day 4 after cell transfer completely ab olished clinical signs of EAE, although comparison of histological fin dings was not remarkable. In conclusion, intrathecal administration of antibodies against LFA-1 and ICAM-1 may be useful for the treatment o f human demyelinating diseases, such as multiple sclerosis. (C) 1996 A cademic Press, Inc.