title: Estradiol treatment redirects the isotype of the autoantibody response and prevents the development of autoimmune arthritis.
abstract: A number of clinical and experimental observations have been made relating elevated estrogen levels with the amelioration of autoimmune diseases, yet questions remain about the levels required for efficacy as well as the mechanism of disease inhibition. Using the collagen-induced arthritis (CIA) model, we have studied the effects of physiological, sustained levels of 17beta-estradiol in preventing the development of autoimmune arthritis and analyzed the changes in the autoimmune response. Using time-release pellets of 17beta-estradiol, arthritis development was significantly inhibited in three different strains of CIA-susceptible mice compared with the effect of placebo treatment, and serum estradiol levels similar to those of mice in estrus were found to be equally effective as higher estradiol concentrations. Analysis of the autoimmune response in the estradiol-treated mice indicated that T cell production of IFN-gamma was markedly decreased, and significant decreases were also observed in levels of IL-10 and GM-CSF produced by lymph nodes cells from estradiol-treated mice. Although the total IgG anti-CII response was only minimally affected by estrogen treatment, a significant reduction in the levels of IgG2a anti-CII Abs and an increase in the levels of IgG1 anti-CII Abs were observed in estradiol-treated mice. These data indicate that estradiol treatment altered the Th profile of the autoimmune T cell response, which, in turn, altered the production of IgG Abs to an isotype that is poor at fixing complement, an important component in the immunopathogenesis of CIA.
authors.affiliation: Veterans Affairs Medical Center, Memphis, TN 38104, USA.
authors.forename: Kary A
authors.initials: KA
authors.lastname: Latham
authors.forename: Alex
authors.initials: A
authors.lastname: Zamora
authors.forename: Heather
authors.initials: H
authors.lastname: Drought
authors.forename: Sandhya
authors.initials: S
authors.lastname: Subramanian
authors.forename: Agata
authors.initials: A
authors.lastname: Matejuk
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
authors.forename: Edward F
authors.initials: EF
authors.lastname: Rosloniec
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000517:prevention & control*; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D002417:Cattle; D024043:Collagen Type II / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D004198:Disease Susceptibility / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis*; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D024043:Collagen Type II; D016207:Cytokines; D004343:Drug Implants; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D004958:Estradiol