title: Oral feeding with ethinyl estradiol suppresses and treats experimental autoimmune encephalomyelitis in SJL mice and inhibits the recruitment of inflammatory cells into the central nervous system.
abstract: There is much interest in the possible ameliorating effects of estrogen on various autoimmune diseases. We previously established the protective effects of 17 beta-estradiol (E2) on experimental autoimmune encephalomyelitis (EAE). In the current study we investigated the effectiveness of oral treatment with ethinyl estradiol (EE) on EAE and the mechanisms involved. Ethinyl estradiol is a semisynthetic estrogen compound found in birth control pills, and its chemical structure allows this compound to retain activity when given orally. We found that oral EE, like E2, drastically suppressed EAE induced by proteolipid protein 139-151 peptide when given at initiation of EAE. However, unlike E2, EE reduced clinical severity when given after the onset of clinical signs. Treatment with EE significantly decreased the secretion of proinflammatory cytokines (IFN-gamma, TNF-alpha, and IL-6) by activated T cells as well as the expression of a key matrix metalloproteinase, disease-mediating chemokines/receptors, and IgG2a levels, but increased the expression of TGF-beta 3 in the CNS. The absence of infiltrating lymphocytes together with the suppression of cytokines, matrix metalloproteinase, and chemokines/receptors suggests that EE, like E2, protects mice from EAE by inhibiting the recruitment of T cells and macrophages into the CNS. These results suggest that oral ethinyl estradiol might be a successful candidate as therapy for multiple sclerosis.
authors.affiliation: Neuroimmunology Research, Veterans Affairs Medical Center, Portland, OR 97201, USA.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Subramanian
authors.forename: Agata
authors.initials: A
authors.lastname: Matejuk
authors.forename: Alex
authors.initials: A
authors.lastname: Zamora
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Vandenbark
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003711:Demyelinating Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D004032:Diet; D015536:Down-Regulation / Q000187:drug effects* / Q000276:immunology; D004334:Drug Administration Schedule; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008815:Mice, Inbred Strains; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D004997:Ethinyl Estradiol