Female BALB/c were sensitized to OVA on days 0 and 7 and subsequently challenged on day 14 over a 3-day period. Mice had their ovaries removed either 7 days before or 8 days after the first OVA injection on day 0.
Pulmonary eosinophilia and AHR were measured 24 h following the last
antigen challenge. In other experiments, ovariectomized mice (Ovx) were pre-treated with
oestradiol benzoate. In further studies, the effect of the
oestradiol antagonist
tamoxifen on allergic
inflammation in intact mice was evaluated. Spleens from all groups were collected for proliferation assays and measurement of
cytokine release.
RESULTS: Removal of the ovaries 7 days before sensitization to OVA significantly inhibited lung
eosinophilia and
IL-5 levels in lung lavage. Furthermore, airway reactivity (maximum response) but not sensitivity (PC100) to
methacholine were significantly reduced in these mice. Proliferation of spleen cells and release of
IL-5 collected from Ovx mice was significantly attenuated compared with spleen cells obtained from non-Ovx mice. Ovx mice treated with
oestradiol benzoate presented partially restored levels of eosinophils and
IL-5 in sensitized mice. Moreover, pharmacological antagonism of the effect of endogenous oestrogen with
tamoxifen significantly reduced the number of eosinophils in the lung of intact sensitized mice, reproducing the effect of
ovariectomy, and suggested a role for oestrogen in the process of
antigen sensitization in female mice. In contrast, removal of ovaries 8 days after the first OVA injection failed to alter significantly
pulmonary eosinophilia or AHR to
methacholine in comparison with non-Ovx mice. Moreover, removal of the ovaries 8 days after the sensitization period induced a significant increase in levels of
IL-5 in lung fluid. Spleen cells collected from these mice also had a significantly higher proliferation index and production of
IL-5 in response to OVA than non-Ovx mice. Treatment with
oestradiol benzoate partially reduced levels of eosinophils present in the lung of Ovx mice, supporting an anti-inflammatory role of
sex hormones during the effector phase of the response to inhaled
antigen.
CONCLUSION: