A protective effect of early pregnancy factor on experimental autoimmune encephalomyelitis induced in Lewis rats by inoculation with myelin basic protein.
Experimental autoimmune encephalomyelitis (EAE) is an organ-specific autoimmune disease characterised by inflammation and demyelination of the central nervous system and is the best available animal model of multiple sclerosis (MS). Since previous studies have shown that EAE is less severe or is delayed in onset during pregnancy and that administration of the pregnancy hormone early pregnancy factor (EPF) down-regulates EAE, experiments in the present study were designed to explore further the role of EPF in EAE. By using the rosette inhibition test, the standard bioassay for EPF and, by semi-quantitative RT-PCR techniques, we have now shown that inflammatory cells from the spinal cord of rats with EAE can produce and secrete EPF, with production being greatest during recovery from disease. Administration of EPF to rats with EAE resulted in a significant increase in the expression of IL-4 and IL-10 mRNA and a significant decrease in IFN-gamma mRNA expression in spinal cord inflammatory cells. Encephalitogenic MBP-specific T cell lines were prepared from popliteal lymph nodes of rats with EAE. Proliferation assays using these cells demonstrated the ability of exogenous EPF to down-regulate the responses of T lymphocytes to MBP.
Harness
Jacqueline
J
Department of Medicine, University of Queensland, Clinical Sciences Building, RoyalBrisbane Hospital, Herston, Queensland 4029, Australia. j.harness@medicine.uq.edu.au
Cavanagh
Alice
A
Morton
Halle
H
McCombe
Pamela
P
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D018835:Chaperonin 10 / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005434:Flow Cytometry; D006168:Guinea Pigs; D006360:Heat-Shock Proteins / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008297:Male; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D011247:Pregnancy; D011257:Pregnancy Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013491:Suppressor Factors, Immunologic; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000954:Antigens, Surface; D018835:Chaperonin 10; D006360:Heat-Shock Proteins; D010455:Peptides; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D013491:Suppressor Factors, Immunologic; C025124:early pregnancy factor; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma