The influence of female sex hormones on the number of alternatively activated lung macrophages and airway inflammation in a mouse model of asthma

The chance of developing asthma increases in girls during puberty. A role for sex hormones has been suggested. Recently we have shown that alternatively activated macrophages (aaMP) contribute to the development of asthma in female mice. Here we have investigated how sex hormone depletion before puberty affects asthma in mice and whether this correlates with aaMP numbers in lung. Female Balb/c mice were ovariectomized (OVX) or sham treated before puberty. OVX animals were left untreated, received a 0.1 mg estrogen (E2) pellet, or a 15 mg progesterone (PG) pellet at the day of OVX (all groups n=8). Four weeks later, mice were sensitized i.p. with ovalbumin (OVA) and alum on days 1 and 7 and challenged with 1% OVA on days 14-20. On day 21, allergic inflammation (OVA-specific IgE, eosinophils) and aaMP numbers were assessed. Ablating sex hormones before puberty significantly increased airway inflammation as judged from higher eosinophil numbers in bronchoalveolar lavage fluid and higher OVA-specific IgE levels in serum. aaMP numbers were unaffected by OVX. Treating OVX mice with E2 significantly reduced eosinophilic airway inflammation with a concomitant reduction in aaMP numbers, whereas PG did not change airway inflammation or aaMP numbers. This study surprisingly shows that OVX in mice before puberty amplifies OVA-induced airway inflammation. This is a consequence of E2 depletion since PG substitution does not reduce the increased allergic inflammation while E2 substitution does. Our data also shows that the effect of OVX does not involve aaMP, whereas reduction of eosinophilic inflammation after E2 substitution appears to involve aaMP.