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      Regulation of Allergic Lung Inflammation in Rats: Interaction between Estradiol and Corticosterone

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          Abstract

          Objective: One third of asthmatic women report a decreased expiratory peak flow during menses. Since asthma is characterized by lung inflammation and bronchopulmonary hyperresponsiveness, we investigated the role played by estradiol in allergic lung inflammation. Methods: Cell migration to the lungs of allergic female rats subjected to oophorectomy (OVx) was compared to that in their sham-operated (sham) control counterparts. Seven days after OVx or sham operation, the rats were sensitized intraperitoneally with ovalbumin (OA, 1 mg/kg) suspended in aluminum hydroxide (day 0). At day 7, a subcutaneous booster of OA was performed and an aerosolized OA challenge was carried out at day 14. One day later (day 15), the rats were killed and cell counts were performed in bronchoalveolar lavages (BAL), in peripheral blood and in bone marrow lavages. Results: After the antigen challenge, OVx rats showed a significant decrease in cell migration to the lung as compared to sham-operated rats. Differential analyses of BAL revealed a reduced number of eosinophils, mononuclear cells and neutrophils. In contrast, in bone marrow as well as in the peripheral blood the numbers of eosinophils, mononuclear cells and neutrophils were increased relative to sham controls. Mast cell numbers were similar in both groups. The estradiol receptor antagonist tamoxifen decreased the allergic lung inflammation in intact rats down to levels similar to those found in untreated OVx rats. In contrast, 17β-estradiol replacement in OVx rats reestablished the allergic lung inflammation, as observed by an elevated number of eosinophils, mononuclear cells and neutrophils recovered in BAL. Similarly, an elevated number of inflammatory cells were quantified in BAL from allergic OVx rats when corticosterone effects were blocked with metyrapone or RU-486. Conclusion: Our results suggest that estradiol has proinflammatory actions on the allergic lung response, and these actions seem to be mediated, at least in part, by endogenous glucocorticoids.

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          Most cited references 9

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          Homologous and heterologous passive cutaneous anaphylactic activity of mouse antisera during the course of immunization.

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            Melatonin modulates allergic lung inflammation.

            Asthma is an inflammatory lung disease characterized by cell migration, bronchoconstriction and hyperresponsiveness, and can be induced, as an experimental model, by ovalbumin sensitization followed by a challenge. In addition to the well-known immunostimulatory effects of melatonin, research has identified some of its anti-inflammatory properties. In this study, we evaluated the influence of pinealectomy and melatonin administration on cell migration in an experimental model of allergic airway inflammation. We evaluated, in pinealectomized rats treated or not with melatonin, cell migration into the bronchoalveolar fluid, the number of cells and their proliferative activity in the bone marrow, and plasma corticosterone levels. Pinealectomy reduces, 24 hr after the challenge, the total cell number count in the lung and bone marrow cell proliferation, without changing the number of cells in the bone marrow or in the peripheral blood. This fact suggests that melatonin is important in the control of cell recruitment from the bone marrow and the migration of those cells to the lung. Melatonin administration to pinealectomized rats seems to restore the ability of cells to migrate from the bone marrow to the bronchoalveolar fluid. So, the development of specific inhibitors of melatonin would benefit patients with asthma.
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              Sex difference in glucocorticoid binding in rat pituitary is estrogen dependent

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                Author and article information

                Journal
                NIM
                Neuroimmunomodulation
                10.1159/issn.1021-7401
                Neuroimmunomodulation
                S. Karger AG
                1021-7401
                1423-0216
                2004
                October 2003
                17 October 2003
                : 11
                : 1
                : 20-27
                Affiliations
                aDepartment of Pharmacology, Institute of Biomedical Sciences and bDepartment of Clinical Analyses, Faculty of Pharmacy, University of São Paulo, São Paulo, Brazil
                Article
                72965 Neuroimmunomodulation 2004;11:20–27
                10.1159/000072965
                14557675
                © 2004 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 4, References: 44, Pages: 8
                Categories
                Original Paper

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