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.

Estrogen Stimulates Th2 Cytokine Production and Regulates the Compartmentalisation of Eosinophils during Allergen Challenge in a Mouse Model of Asthma

“…However, the role of estrogen in allergic inflammation is controversial with studies such as those by Dimitropoulou et al [6] showing that implantation of estradiol pellets in OVX mice before sensitisation reduced airway inflammation. The use of models employing OVX to study the role of estrogen in allergic inflammation is complicated because ovarian products other than estrogen may influence the observed effects [7]. Indeed, a recent study suggested an important consideration when analysing the role of sex hormones in allergic disease is not the levels of circulating estrogen per se, but the estrogen/progesterone ratio [7].…”

“…The use of models employing OVX to study the role of estrogen in allergic inflammation is complicated because ovarian products other than estrogen may influence the observed effects [7]. Indeed, a recent study suggested an important consideration when analysing the role of sex hormones in allergic disease is not the levels of circulating estrogen per se, but the estrogen/progesterone ratio [7]. In congruence with this concept, estradiol supplementation of OVX mice does not fully compensate the anti-inflammatory effects of OVX in allergic airway disease [5].…”

Characteristics of Asthma Patients Seeking Care at West Java’s Top Referral Hospital, Indonesia

“…The expression of Interleukin (IL) like IL-10, IL1-β, and Tumor Necrosis Factor (TNF)-α will increase by the effect of progesterone. 12 Female hormones also have an impact on T helper cell. 11 Females have a better humoral immunity than males, who demonstrate a better cellular immunity.…”

Effects of prone and supine position on oxygenation and inflammatory mediator in a hydrochloric acid-induced lung dysfunction in rats

“…TNF-α is an early-response, pro-inflammatory cytokine that has been shown to be integral in the pathogenesis of other lung injury models that are neutrophil-mediated [17][18][19][20] . TNF-α leads to activation of leukocytes and induces the expression of endothelial adhesion molecules that play a major role in the leukocyte-endothelial interactions that lead to neutrophil migration into the alveoli 21 .…”