Early pregnancy factor suppresses experimental autoimmune encephalomyelitis induced in Lewis rats with myelin basic protein and in SJL/J mice with myelin proteolipid protein peptide 139-151.
Early pregnancy factor (EPF) is a secreted protein with immunosuppressive and growth factor properties. During pregnancy, it appears in maternal serum within 6-24 h of fertilization, is present for at least the first two-thirds of pregnancy in all species studied and is essential for embryonic survival. It is a homologue of chaperonin 10, a heat shock protein, but, unlike other members of this family, EPF has an extracellular role. As it has the ability to modulate CD4+ T cell-dependent immune responses, its role in treatment of experimental autoimmune encephalomyelitis (EAE) was investigated. EAE is a CD4+ T cell-mediated disease, the best available animal model of multiple sclerosis (MS). Two models of EAE were investigated, acute EAE induced in Lewis rats by inoculation with myelin basic protein (MBP-EAE) and chronic relapsing EAE induced in SJL/J mice by inoculation with myelin proteolipid protein peptide (residues 139-151) (PLP-EAE). EPF, delivered intraperitoneally or orally to rats or intraperitoneally to mice, suppressed clinical signs of disease. Mice with PLP-EAE were also treated with interferon-beta, with and without EPF. Both EPF and IFN-beta suppressed clinical signs of EAE and, when administered together, gave greater suppression than when given separately. These findings suggest that EPF may be a potential candidate for use in treatment of MS and may be of use in combined therapy with IFN-beta.
Zhang
B
B
Department of Surgery, The University of Queensland, Royal Brisbane Hospital, 4029, Queensland, Australia.
Harness
J
J
Somodevilla-Torres
M J
MJ
Hillyard
N C
NC
Mould
A W
AW
Alewood
D
D
Love
S G
SG
Alewood
P F
PF
Greer
J M
JM
Cavanagh
A C
AC
McCombe
P A
PA
Morton
H
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D018835:Chaperonin 10; D004353:Drug Evaluation, Preclinical; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D011247:Pregnancy; D011257:Pregnancy Proteins; D051381:Rats; D011917:Rats, Inbred Lew; D013491:Suppressor Factors, Immunologic
D000276:Adjuvants, Immunologic; D018835:Chaperonin 10; D007166:Immunosuppressive Agents; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D010455:Peptides; D011257:Pregnancy Proteins; D013491:Suppressor Factors, Immunologic; C025124:early pregnancy factor; D016899:Interferon-beta