2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece.
Department of Cytopathology, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece.
Cytokine. 2018 Feb;102:168-172. doi: 10.1016/j.cyto.2017.08.019. Epub 2017 Aug 25.
Controversy exists about the pathogenesis of idiopathic pulmonary fibrosis acute exacerbations (IPF-AEs). According to one hypothesis IPF-AEs represent the development of any etiology diffuse alveolar damage (DAD) upon usual interstitial pneumonia (UIP), whilst other researchers argue that an accelerated phase of the intrinsic fibrotic process of unknown etiology prevails, leading to ARDS. Different cytokines might be involved in both processes. The aim of this study was to assess pro-inflammatory and pro-fibrotic cytokines in the peripheral blood from stable and exacerbated IPF patients.
Consecutive IPF patients referred to our department were included. Diagnoses of IPF and IPF-AE were based on international guidelines and consensus criteria. The interleukins (IL)-4, IL-6, IL-8, IL-10, and IL-13 as well asactive transforming growth factor-beta (TGF-β) were measured in blood from both stable and exacerbated patients on the day of hospital admission for deterioration. Subjects were followed for 12months. Mann-Whitney test as well as Tobit and logistic regression analyses were applied.
Among the 41 patients studied, 23 were stable, and 18 under exacerbation; of the latter, 12 patients survived. The IL-6 and IL-8 levels were significantly higher in exacerbated patients (p=0.002 and p=0.046, respectively). An increase in either IL-6 or IL-8 by 1pg/ml increases the odds of death by 5.6% (p=0.021) and 6.7% (p=0.013), respectively, in all patients. No differences were detected for the other cytokines.
High levels of IL-6 and IL-8 characterize early-on IPF-AEs and an increase in the levels of IL-6 and IL-8 associates with worse outcome in all patients. However, as the most representative pro-fibrotic cytokines, TGF-β, IL-10, IL-4 and IL-13 were not increased and given the dualistic nature, both pro-inflammatory and pro-fibrotic of IL-6 further studies are necessary to clarify the enigma of IPF-AEs etiopathogenesis.
特发性肺纤维化急性加重（IPF-AE）的发病机制存在争议。根据一种假说，IPF-AE 代表通常间质肺炎（UIP）基础上任何病因弥漫性肺泡损伤（DAD）的发展，而其他研究人员则认为未知病因的内在纤维化过程加速占主导地位，导致急性呼吸窘迫综合征（ARDS）。不同的细胞因子可能参与这两个过程。本研究旨在评估稳定期和加重期 IPF 患者外周血中的促炎和促纤维化细胞因子。
连续纳入我院就诊的 IPF 患者。IPF 和 IPF-AE 的诊断基于国际指南和共识标准。在病情恶化时入院当天测量稳定期和加重期患者外周血中的白细胞介素（IL）-4、IL-6、IL-8、IL-10 和 IL-13 以及活性转化生长因子-β（TGF-β）。对患者进行 12 个月的随访。采用 Mann-Whitney 检验、Tobit 和逻辑回归分析。
在研究的 41 名患者中，23 名处于稳定期，18 名处于加重期；其中 12 名加重期患者存活。加重期患者的 IL-6 和 IL-8 水平明显升高（p=0.002 和 p=0.046）。IL-6 或 IL-8 每增加 1pg/ml，所有患者的死亡风险分别增加 5.6%（p=0.021）和 6.7%（p=0.013）。其他细胞因子无差异。
高水平的 IL-6 和 IL-8 是 IPF-AE 的早期特征，IL-6 和 IL-8 水平的增加与所有患者的预后不良相关。然而，作为最具代表性的促纤维化细胞因子，TGF-β、IL-10、IL-4 和 IL-13 并未增加，鉴于 IL-6 的双重特性，既具有促炎作用又具有促纤维化作用，因此需要进一步研究来阐明 IPF-AE 发病机制的谜团。
