Møller Rikke, Uhre Nielsen Bibi, Rossi Elio, Lausen Mads, Skov Marianne, Pressler Tacjana, Ostrowski Sisse Rye, Johansen Helle Krogh
Cystic Fibrosis Centre Copenhagen, Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
These authors contributed equally.
ERJ Open Res. 2024 Aug 27;10(4). doi: 10.1183/23120541.00256-2024. eCollection 2024 Jul.
Lung disease progression in people with cystic fibrosis (pwCF) varies from one individual to another. Different immunological characteristics have been suggested to explain this variation, and we hypothesised that lung capacity may be associated with the innate immune response in pwCF. In an exploratory study, we aimed to investigate potential links between the innate immune response and lung function in pwCF using the standardised immune function assay TruCulture.
In a single-centre study with combined cross-sectional and longitudinal data before and after intravenous antibiotics, blood was sampled from -infected pwCF. Whole blood was analysed by TruCulture to reveal the unstimulated and stimulated cytokine release. Tobit regressions and Spearman's correlations were used to estimate the associations between lung function and cytokine release.
We included 52 pwCF in the cross-sectional study and 24 in the longitudinal study. In the cross-sectional study, we found that compared to a healthy population, the release of toll-like receptor (TLR)3, TLR4- and TLR7/8-stimulated interferon-γ, and interleukin (IL)-12p40 was reduced. Although TLR3-stimulated IL-1β and IL-6 release increased with lung function, overall, cytokine release did not correlate well with lung function. In the longitudinal study, the cytokine release was modified by antibiotic treatment, but the cytokine release before antibiotic treatment did not associate with changes in lung function after treatment.
The stimulated cytokine release could not predict lung function levels or changes in pwCF, but our data indicate that pwCF experience exhaustion in the innate immune response after years of chronic bacterial infection.
囊性纤维化患者（pwCF）的肺部疾病进展因人而异。已有不同的免疫特征被提出用以解释这种差异，并且我们推测肺容量可能与pwCF的先天免疫反应相关。在一项探索性研究中，我们旨在使用标准化免疫功能检测方法TruCulture来研究pwCF的先天免疫反应与肺功能之间的潜在联系。
在一项单中心研究中，收集静脉使用抗生素前后的横断面和纵向数据，从受感染的pwCF患者中采集血液样本。通过TruCulture分析全血，以揭示未刺激和刺激后的细胞因子释放情况。使用 Tobit 回归和 Spearman 相关性分析来估计肺功能与细胞因子释放之间的关联。
横断面研究纳入了52例pwCF患者，纵向研究纳入了24例。在横断面研究中，我们发现与健康人群相比，Toll样受体（TLR）3、TLR4以及TLR7/8刺激后的干扰素-γ和白细胞介素（IL）-12p40的释放减少。尽管TLR3刺激后的IL-1β和IL-6释放随肺功能增加，但总体而言，细胞因子释放与肺功能的相关性不佳。在纵向研究中，细胞因子释放受到抗生素治疗的影响，但抗生素治疗前的细胞因子释放与治疗后肺功能的变化无关。
刺激后的细胞因子释放无法预测pwCF的肺功能水平或变化，但我们的数据表明，经过多年慢性细菌感染后，pwCF患者的先天免疫反应出现耗竭。
