title: Cellular recruitment and cytokine generation in a rat model of allergic lung inflammation are differentially modulated by progesterone and estradiol.
abstract: 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.
authors.affiliation: 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 (SP05508-900, Brazil.
authors.forename: Ana Paula Ligeiro
authors.initials: AP
authors.lastname: de Oliveira
authors.forename: Helori Vanni
authors.initials: HV
authors.lastname: Domingos
authors.forename: Gabriela
authors.initials: G
authors.lastname: Cavriani
authors.forename: Amilcar Sabino
authors.initials: AS
authors.lastname: Damazo
authors.forename: Adriana Lino
authors.initials: AL
authors.lastname: Dos Santos Franco
authors.forename: Sonia Maria
authors.initials: SM
authors.lastname: Oliani
authors.forename: Ricardo Martins
authors.initials: RM
authors.lastname: Oliveira-Filho
authors.forename: Bernardo Boris
authors.initials: BB
authors.lastname: Vargaftig
authors.forename: Wothan Tavares
authors.initials: WT
authors.lastname: de Lima
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004958:Estradiol / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D006967:Hypersensitivity / Q000276:immunology / Q000503:physiopathology; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007958:Leukocyte Count; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D010052:Ovariectomy; D011014:Pneumonia / Q000276:immunology* / Q000503:physiopathology*; D011374:Progesterone / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D011374:Progesterone; D004958:Estradiol; D010047:Ovalbumin