Southcott A M, Jones K P, Li D, Majumdar S, Cambrey A D, Pantelidis P, Black C M, Laurent G J, Davies B H, Jeffery P K
Interstitial Lung Disease Unit, Royal Brompton National Heart and Lung Hospital, London, England.
Am J Respir Crit Care Med. 1995 May;151(5):1604-12. doi: 10.1164/ajrccm.151.5.7735620.
Fibrosing alveolitis may occur alone (CFA) or in association with systemic sclerosis (FASSc). FASSc was recently shown to have a prognostic advantage over CFA. Because interleukin-8 (IL-8) is likely to be a major determinant of neutrophil alveolitis, we evaluated IL-8 expression in patients with CFA and FASSc and compared it with that in normal individuals and sarcoidosis and systemic sclerosis patients without pulmonary involvement (SSc no FA). IL-8 protein in bronchoalveolar lavage fluid (BALF) was assessed by immunoassay, and IL-8 mRNA expression was assessed using Northern analysis and reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization of lung parenchyma. Compared with normal subjects, IL-8 concentration was significantly greater in both CFA (p < 0.001) and FASSc groups (p < 0.05) but no different in sarcoidosis. The IL-8 concentration in CFA was higher than in FASSc (p < 0.01) and was related to BAL % neutrophils (rs = 0.48, p < 0.01). IL-8 mRNA expression evaluated by Northern analysis was seen only in patients with CFA and FASSc and was related to BAL % neutrophils (rs = 0.63, p < 0.01). We suggest that IL-8 is a key factor in the pathogenesis of fibrosing alveolitis and that the poorer prognosis of CFA compared with FASSc is related to higher levels of IL-8 within the lower respiratory tract.
纤维化肺泡炎可单独发生(隐源性纤维化肺泡炎,CFA)或与系统性硬化症相关(系统性硬化症相关纤维化肺泡炎,FASSc)。最近研究表明,FASSc的预后优于CFA。由于白细胞介素-8(IL-8)可能是中性粒细胞肺泡炎的主要决定因素,我们评估了CFA和FASSc患者的IL-8表达,并将其与正常个体、结节病患者以及无肺部受累的系统性硬化症患者(系统性硬化症无纤维化肺泡炎,SSc no FA)进行比较。通过免疫测定法评估支气管肺泡灌洗液(BALF)中的IL-8蛋白,使用Northern印迹分析、逆转录-聚合酶链反应(RT-PCR)以及肺实质的原位杂交来评估IL-8 mRNA表达。与正常受试者相比,CFA组(p < 0.001)和FASSc组(p < 0.05)的IL-8浓度均显著升高,但结节病患者无差异。CFA组的IL-8浓度高于FASSc组(p < 0.01),且与BAL中性粒细胞百分比相关(rs = 0.48,p < 0.01)。通过Northern印迹分析评估的IL-8 mRNA表达仅在CFA和FASSc患者中可见,且与BAL中性粒细胞百分比相关(rs = 0.63,p < 0.01)。我们认为,IL-8是纤维化肺泡炎发病机制中的关键因素,与FASSc相比,CFA预后较差与下呼吸道中较高水平的IL-8有关。