Applied Biomedical Research & Training Center Marianthi Simou, Department of Critical Care & Pulmonary Services, General Hospital Evangelismos, School of Medicine, National and Kapodistrian University of Athens, 3 Ploutarhou Str, 10675 Athens, Greece.
Respir Res. 2010 Aug 26;11(1):118. doi: 10.1186/1465-9921-11-118.
Although the relationship between allergic inflammation and lung carcinogenesis is not clearly defined, several reports suggest an increased incidence of lung cancer in patients with asthma. We aimed at determining the functional impact of allergic inflammation on chemical carcinogenesis in the lungs of mice.
Balb/c mice received single-dose urethane (1 g/kg at day 0) and two-stage ovalbumin during tumor initiation (sensitization: days -14 and 0; challenge: daily at days 6-12), tumor progression (sensitization: days 70 and 84; challenge: daily at days 90-96), or chronically (sensitization: days -14 and 0; challenge: daily at days 6-12 and thrice weekly thereafter). In addition, interleukin (IL)-5 deficient and wild-type C57BL/6 mice received ten weekly urethane injections. All mice were sacrificed after four months. Primary end-points were number, size, and histology of lung tumors. Secondary end-points were inflammatory cells and mediators in the airspace compartment.
Ovalbumin provoked acute allergic inflammation and chronic remodeling of murine airways, evident by airspace eosinophilia, IL-5 up-regulation, and airspace enlargement. Urethane resulted in formation of atypical alveolar hyperplasias, adenomas, and adenocarcinomas in mouse lungs. Ovalbumin-induced allergic inflammation during tumor initiation, progression, or continuously did not impact the number, size, or histologic distribution of urethane-induced pulmonary neoplastic lesions. In addition, genetic deficiency in IL-5 had no effect on urethane-induced lung tumorigenesis.
Allergic inflammation does not impact chemical-induced carcinogenesis of the airways. These findings suggest that not all types of airway inflammation influence lung carcinogenesis and cast doubt on the idea of a mechanistic link between asthma and lung cancer.
尽管过敏炎症与肺癌发生之间的关系尚未明确界定，但有几项报告表明哮喘患者的肺癌发病率增加。我们旨在确定过敏炎症对小鼠肺部化学致癌作用的功能影响。
Balb/c 小鼠在肿瘤起始时接受单次剂量的尿嘧啶（第 0 天 1 克/千克）和两阶段卵清蛋白（致敏：第-14 天和 0 天；挑战：第 6-12 天每天；进展：致敏：第 70 天和 84 天；挑战：第 90-96 天每天），或慢性（致敏：第-14 天和 0 天；挑战：第 6-12 天，然后每周三次）。此外，白细胞介素（IL）-5 缺陷和野生型 C57BL/6 小鼠接受了十次每周尿嘧啶注射。所有小鼠在四个月后被处死。主要终点是肺肿瘤的数量、大小和组织学。次要终点是气腔隔室中的炎症细胞和介质。
卵清蛋白引发了小鼠气道的急性过敏炎症和慢性重塑，表现为气腔嗜酸性粒细胞增多、IL-5 上调和气腔扩大。尿嘧啶导致小鼠肺部形成非典型肺泡增生、腺瘤和腺癌。在肿瘤起始、进展或连续期间，卵清蛋白诱导的过敏炎症不会影响尿嘧啶诱导的肺部肿瘤病变的数量、大小或组织学分布。此外，IL-5 的基因缺失对尿嘧啶诱导的肺肿瘤发生没有影响。
过敏炎症不会影响气道的化学致癌作用。这些发现表明，并非所有类型的气道炎症都会影响肺癌发生，并对哮喘与肺癌之间存在机制联系的观点提出了质疑。
