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Am J Physiol Cell Physiol 293: C1120-C1128, 2007. First published July 18, 2007; doi:10.1152/ajpcell.00286.2006
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RECEPTORS AND SIGNAL TRANSDUCTION

Cellular recruitment and cytokine generation in a rat model of allergic lung inflammation are differentially modulated by progesterone and estradiol

Ana Paula Ligeiro de Oliveira,1 Helori Vanni Domingos,1 Gabriela Cavriani,1 Amilcar Sabino Damazo,2 Adriana Lino dos Santos Franco,1 Sonia Maria Oliani,2 Ricardo Martins Oliveira-Filho,1 Bernardo Boris Vargaftig,1 and Wothan Tavares de Lima1

1Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo; and 2Department of Biology, Institute of Biosciences, Language Studies and Exact Sciences, São Paulo State University, São José do Rio Preto, Brazil

Submitted 23 May 2006 ; accepted in final form 28 June 2007

We evaluated the role of estradiol and progesterone in allergic lung inflammation. Rats were ovariectomized (Ovx) and, 7 days later, were sensitized with ovalbumin (OA) and challenged after 2 wk with inhaled OA; experiments were performed 1 day thereafter. Ovx-allergic rats showed reduced cell recruitment into the bronchoalveolar lavage (BAL) fluid relative to sham-Ovx allergic rats, as was observed in intact allergic rats treated with ICI-182,780. Estradiol increased the number of cells in the BAL of Ovx-allergic rats, whereas progesterone induced an additional reduction. Cells of BAL and bone marrow (BM) of Ovx-allergic rats released elevated amounts of IL-10 and reduced IL-1beta and TNF-{alpha}. BM cells of Ovx-allergic rats released increased amounts of IL-10 and lower amounts of IL-4. Estradiol treatment of Ovx-allergic rats decreased the release of IL-10 but increased that of IL-4 by BM cells. Estradiol also caused an increased release of IL-1beta and TNF-{alpha} by BAL cells. Progesterone significantly increased the release of IL-10, IL-1beta, and TNF-{alpha} by BAL cells and augmented that of IL-4 by BM cells. Degranulation of bronchial mast cells from Ovx rats was reduced after in vitro challenge, an effect reverted by estradiol but not by progesterone. We suggest that the serum estradiol-to-progesterone ratio might drive cellular recruitment, modulating the pulmonary allergy and profile of release of anti-inflammatory or inflammatory cytokines. The existence of such dual hormonal effects suggests that the hormone therapy of asthmatic postmenopausal women and of those suffering of premenstrual asthma should take into account the possibility of worsening the pulmonary conditions.

asthma; eosinophils



Address for reprint requests and other correspondence: W. Tavares de Lima, Av. Prof. Lineu Prestes, 1524, Lab. Fisiopatologia da Inflamação Experimental, Instituto de Ciências Biomédicas, Universidade de São Paulo, Departamento de Farmacologia, Cidade Universitária, São Paulo (SP) 05508-900, Brazil (e-mail: wtdelima{at}icb.usp.br)




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