Riffo-Vasquez Y, Ligeiro de Oliveira A P, Page C P, Spina D, Tavares-de-Lima W
The Sackler Institute of Pulmonary Pharmacology, King's College London, London, UK.
Clin Exp Allergy. 2007 Mar;37(3):459-70. doi: 10.1111/j.1365-2222.2007.02670.x.
A number of clinical studies have documented both a pro- and anti-inflammatory role for sex hormones in the context of lung inflammation and worsening of asthma.
To determine the role of sex hormones in a murine model of allergic inflammation and airway hyper-responsiveness (AHR) induced by ovalbumin (OVA).
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.
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.
Sex hormones play a dual role in regulating allergic lung inflammation in mice.
多项临床研究记录了性激素在肺部炎症和哮喘恶化过程中既具有促炎作用又具有抗炎作用。
确定性激素在卵清蛋白（OVA）诱导的过敏性炎症和气道高反应性（AHR）小鼠模型中的作用。
雌性BALB/c小鼠在第0天和第7天对OVA进行致敏，随后在第14天进行为期3天的激发。在第0天首次注射OVA前7天或注射后8天切除小鼠卵巢。在最后一次抗原激发后24小时测量肺部嗜酸性粒细胞增多和AHR。在其他实验中，对去卵巢小鼠（Ovx）用苯甲酸雌二醇进行预处理。在进一步的研究中，评估了雌激素拮抗剂他莫昔芬对完整小鼠过敏性炎症的影响。收集所有组的脾脏用于增殖测定和细胞因子释放的测量。
在对OVA致敏前7天切除卵巢可显著抑制肺部嗜酸性粒细胞增多和肺灌洗中的IL-5水平。此外，这些小鼠对乙酰甲胆碱的气道反应性（最大反应）而非敏感性（PC100）显著降低。与从非Ovx小鼠获得的脾细胞相比，从Ovx小鼠收集的脾细胞增殖和IL-5释放显著减弱。用苯甲酸雌二醇处理的Ovx小鼠在致敏小鼠中呈现出部分恢复的嗜酸性粒细胞和IL-5水平。此外，用他莫昔芬对内源性雌激素的作用进行药理拮抗可显著减少完整致敏小鼠肺部的嗜酸性粒细胞数量，重现了去卵巢的效果，并提示雌激素在雌性小鼠抗原致敏过程中起作用。相比之下，在首次注射OVA后8天切除卵巢与非Ovx小鼠相比，未能显著改变肺部嗜酸性粒细胞增多或对乙酰甲胆碱的AHR。此外，在致敏期后8天切除卵巢导致肺液中IL-5水平显著升高。从这些小鼠收集的脾细胞对OVA的增殖指数和IL-5产生也显著高于非Ovx小鼠。用苯甲酸雌二醇处理可部分降低Ovx小鼠肺部存在的嗜酸性粒细胞水平，支持性激素在对吸入抗原反应的效应阶段具有抗炎作用。
性激素在调节小鼠过敏性肺部炎症中起双重作用。
