al-Sabbagh A M, Goad E P, Weiner H L, Nelson P A
AutoImmune Inc, Lexington, MA 02173, USA.
J Neurosci Res. 1996 Aug 15;45(4):424-9. doi: 10.1002/(SICI)1097-4547(19960815)45:4<424::AID-JNR11>3.0.CO;2-0.
Murine chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE) is a model of inflammatory demyelinating disease of the central nervous system (CNS) with similarity to multiple sclerosis (MS) in humans. Mice with confirmed neurologic deficits from CR-EAE were treated by oral administration of whole bovine myelin to investigate the effect of long-term oral delivery of myelin antigens on clinical disease and on the inflammatory response in the CNS. EAE-positive mice were fed doses of 1 mg, 10 mg, or 20 mg of bovine myelin every other day for 6 months. We found that prolonged oral delivery of neuroantigen suppressed inflammatory and demyelination foci in the CNS of myelin-treated mice with no exacerbation of clinical disease status compared with the control group. Analysis of histologic sections of brain and spinal cords with hematoxylin-eosin (H&E) and Luxol fast blue (LFB) staining showed a decrease in the inflammatory cell infiltration and active centers of demyelination, respectively. Furthermore, after 6 months of treatment, there was no increased sensitization to myelin antigens seen, as measured by antimyelin basic protein (MBP) or anti-proteolipid apoprotein (PLP) antibodies. These results demonstrate that prolonged oral administration of myelin antigens in diseased animals has an ameliorating effect on the pathologic process and supports its potential long-term use in humans with MS.