title: Prolactin in combination with interferon-β reduces disease severity in an animal model of multiple sclerosis.
abstract: Previous work has demonstrated that the hormone prolactin promotes oligodendrocyte precursor proliferation and remyelination following lysolecithin-induced demyelination of the mouse spinal cord. Prolactin, however, can elicit pro-inflammatory responses, and its use in the prototypical demyelinating and inflammatory condition, multiple sclerosis (MS), should thus be approached cautiously. Here, we sought to determine whether recombinant prolactin could alter the course of experimental autoimmune encephalomyelitis (EAE), an inflammatory animal model of MS. Consistent with previous literature, we found that prolactin activated leukocytes in vitro. Daily treatment with prolactin from around the time of onset of clinical signs, for 9 (days 9 to 17) or 25 (days 9 to 33) days did not increase clinical or histological signs of EAE over that of vehicle-treated mice. Instead, the combination of prolactin and a suboptimal dose of recombinant murine interferon-β resulted in (days 9 to 17 group) or trended towards (days 9 to 33 group), a greater amelioration of clinical signs of EAE, compared to either treatment alone or to vehicle controls. Histological analyses corroborated the clinical EAE data. These results suggest that prolactin may be beneficial when administered in combination with interferon-β in MS.
authors.affiliation: Hotchkiss Brain Institute and the Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada. simon.zhornitsky@albertahealthservices.ca.
authors.forename: Simon
authors.initials: S
authors.lastname: Zhornitsky
authors.affiliation: Hotchkiss Brain Institute and the Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada. trina.johnson@mcgill.ca.
authors.forename: Trina A
authors.initials: TA
authors.lastname: Johnson
authors.affiliation: Hotchkiss Brain Institute and the Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada. luanne.metz@albertahealthservices.ca.
authors.forename: Luanne M
authors.initials: LM
authors.lastname: Metz
authors.affiliation: Hotchkiss Brain Institute and the Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada. weiss@ucalgary.ca.
authors.forename: Samuel
authors.initials: S
authors.lastname: Weiss
authors.affiliation: Hotchkiss Brain Institute and the Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada. vyong@ucalgary.ca.
authors.forename: V Wee
authors.initials: VW
authors.lastname: Yong
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D010446:Peptide Fragments / Q000633:toxicity; D011388:Prolactin / Q000627:therapeutic use*; D013116:Spinal Cord / Q000473:pathology; D013997:Time Factors
chemical_list: D007155:Immunologic Factors; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D016899:Interferon-beta; D011388:Prolactin