Estradiol treatment redirects the isotype of the autoantibody response and prevents the development of autoimmune arthritis
| Autor: | Edward F. Rosloniec, Kary A. Latham, Sandhya Subramanian, Heather Drought, Alex Zamora, Halina Offner, Agata Matejuk |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class T cell T-Lymphocytes Immunology Arthritis Down-Regulation Mice Transgenic Disease Autoimmune Diseases Mice Internal medicine medicine Immunology and Allergy Animals Humans Collagen Type II Autoantibodies Estrous cycle Drug Implants Estradiol business.industry Immunodominant Epitopes medicine.disease Isotype Arthritis Experimental Immunoglobulin Isotypes medicine.anatomical_structure Endocrinology Estrogen Mice Inbred DBA Immunoglobulin G Disease Progression Cytokines Cattle Lymph Disease Susceptibility business Estradiol treatment hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 171(11) |
| ISSN: | 0022-1767 |
| Popis: | 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 17β-estradiol in preventing the development of autoimmune arthritis and analyzed the changes in the autoimmune response. Using time-release pellets of 17β-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-γ 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. |
| Databáze: | OpenAIRE |
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