Muhlebach Marianne S, Reed William, Noah Terry L
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7220, USA.
Pediatr Pulmonol. 2004 May;37(5):393-9. doi: 10.1002/ppul.20010.
Bronchoalveolar lavage fluid (BALF) in cystic fibrosis (CF) shows increased inflammation, which could be due to abnormal cytokine regulation. Bronchial epithelial cells and migratory inflammatory cells produce these cytokines, but few quantitative in vivo data are available comparing young CF patients with controls. We hypothesized that IL-8 mRNA abundance was higher in young CF vs. non-CF disease control patients in lung epithelium and inflammatory cells. Bronchial epithelial cells (BEC) were obtained by brush biopsy, and airway inflammatory cells (BALFC) by bronchoalveolar lavage, in 17 CF and 21 non-CF patients <5 years old undergoing clinically indicated bronchoscopy. Cellular mRNA expression was quantified by real-time PCR and normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Abundance of IL-8/GAPDH in BEC was significantly higher in CF (14.8 +/- 3.3) than non-CF (4.2 +/- 0.6) samples, and this difference was also significant when patients were stratified according to infection. In BALFC, the difference in IL-8 expression did not reach statistical significance: CF (17.1 +/- 6.5) vs. non-CF (6.8 +/- 1.9), but BALF cell number/ml was significantly higher in CF. IL-10 mRNA was very low in all samples, without showing a decrease in CF vs. non-CF patients. We conclude that early in the disease, IL-8 mRNA expression in BEC is increased in CF in vivo. Although IL-8 mRNA in migratory cells was not significantly higher in CF, these cells may still contribute to elevated IL-8 in airway secretions, secondary to increased cell density in BALF.
囊性纤维化(CF)患者的支气管肺泡灌洗液(BALF)显示炎症增加,这可能是由于细胞因子调节异常所致。支气管上皮细胞和迁移性炎症细胞产生这些细胞因子,但比较年轻CF患者与对照组的体内定量数据很少。我们假设,与非CF疾病对照患者相比,年轻CF患者肺上皮和炎症细胞中的白细胞介素-8(IL-8)信使核糖核酸(mRNA)丰度更高。对17例CF患者和21例年龄<5岁、因临床需要接受支气管镜检查的非CF患者,通过刷检获取支气管上皮细胞(BEC),通过支气管肺泡灌洗获取气道炎症细胞(BALFC)。通过实时聚合酶链反应(PCR)对细胞mRNA表达进行定量,并以甘油醛-3-磷酸脱氢酶(GAPDH)进行标准化。CF患者BEC中IL-8/GAPDH的丰度(14.8±3.3)显著高于非CF患者(4.2±0.6),根据感染情况对患者进行分层时,这种差异也很显著。在BALFC中,IL-8表达的差异未达到统计学意义:CF患者为(17.1±6.5),非CF患者为(6.8±1.9),但CF患者的BALF细胞数/毫升显著更高。所有样本中白细胞介素-10(IL-10)mRNA水平都很低,CF患者与非CF患者之间没有下降。我们得出结论,在疾病早期,CF患者体内BEC中的IL-8 mRNA表达增加。虽然CF患者迁移细胞中的IL-8 mRNA没有显著升高,但由于BALF中细胞密度增加,这些细胞可能仍导致气道分泌物中IL-8升高。