Progesterone increases airway eosinophilia and hyper-responsiveness in a murine model of allergic asthma

Authors


Jan Ceuppens, Laboratory of Experimental Immunology, Onderwijs en Navorsing, U.Z. Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. E-mail: Jan.Ceuppens@med.kuleuven.ac.be

Summary

Background Sex hormones might affect the severity and evolution of bronchial asthma. From existing literature, there exists, however, no convincing evidence for either exacerbation or improvement of allergic symptoms by progesterone.

Objective This study was aimed to explore the effect of exogenously administered progesterone in a mouse model of allergic asthma.

Methods BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injections with OVA followed by chronic inhalation of nebulized OVA or physiologic saline (Sal). Medroxyprogesterone acetate or placebo was instilled daily into the oesophagus before and during the inhalatory OVA challenge phase.

Results Progesterone worsened allergic airway inflammation in OVA-challenged mice, as evidenced by enhanced bronchial responsiveness to inhaled metacholine and increased bronchial eosinophilia. Elevated airway eosinophilia corresponded with higher bronchial and systemic IL-5 levels in the progesterone group. The ratio of IL-4/IFN-γ levels in bronchoalveolar lavage fluid and numbers of eosinophil colony-forming units in the bone marrow were also elevated in the latter group. Progesterone, however, did not influence allergen-specific IgE production, nor did it affect bronchial responses in Sal-challenged mice.

Conclusion Our data show that exogenously administered progesterone aggravates the phenotype of eosinophilic airway inflammation in mice by enhancing systemic IL-5 production. Progesterone also increases bronchial hyper-reactivity.

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