肿瘤坏死因子-α和白细胞介素-1β与 HIV 感染者肺气肿的独立相关性。
Independent Associations of Tumor Necrosis Factor-Alpha and Interleukin-1 Beta With Radiographic Emphysema in People Living With HIV.
机构信息
Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Infectious Diseases, Copenhagen University Hospital - Amager and Hvidovre Hospital, Hvidovre, Denmark.
出版信息
Front Immunol. 2021 Apr 14;12:668113. doi: 10.3389/fimmu.2021.668113. eCollection 2021.
BACKGROUND
People living with HIV (PLWH) have increased systemic inflammation, and inflammation has been suggested to contribute to the pathogenesis of emphysema. We investigated whether elevated cytokine concentrations (interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor-alpha (TNFα), interferon-gamma (IFNγ), soluble CD14 (sCD14) and sCD163 were independently associated with radiographic emphysema in PLWH.
METHODS
We included PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study without hepatitis B and C co-infection and with a plasma sample and a chest computed tomography scan available. Emphysema plus trace emphysema was defined as the percentage of low attenuation area under -950 Houndsfield Unit (%LAA-950) using a cut-off at 5%. Cytokine concentrations were measured by ELISA or Luminex immunoassays. An elevated cytokine concentration was defined as above the 75 percentile.
RESULTS
Of 783 PLWH, 147 (18.8%) had emphysema. PLWH were predominantly male (86.0%) and 743 (94.9%) had undetectable viral replication. PLWH with emphysema had higher concentrations of TNFα (median (IQR): 8.2 (6.4-9.8) versus 7.1 (5.7-8.6) pg/ml, p<0.001), IL-1β (0.21 (0.1-0.4) versus 0.17 (0.1-0.3) pg/ml, p=0.004) and IL-6 (3.6 (2.6-4.9) versus 3.1 (2.0-4.3) pg/ml, p=0.023) than PLWH without. In a logistic regression model adjusted for age, sex, ethnicity, smoking status, BMI and CD4 nadir, elevated TNFα (adjusted odds ratio (aOR): 1.78 [95%CI: 1.14-2.76], p=0.011) and IL-1β (aOR: 1.81 [95%CI: 1.16-2.81], p=0.009) were independently associated with emphysema. The association between IL-1β and emphysema was modified by smoking (p-interaction=0.020) with a more pronounced association in never-smokers (aOR: 4.53 [95%CI: 2.05-9.98], p<0.001).
CONCLUSION
Two markers of systemic inflammation, TNFα and IL-1β, were independently associated with emphysema in PLWH and may contribute to the pathogenesis of emphysema. Importantly, the effect of IL-1β seems to be mediated through pathways that are independent of excessive smoking.
CLINICAL TRIAL REGISTRATION
clinicaltrials.gov, identifier NCT02382822.
背景
HIV 感染者（PLWH）存在全身炎症增加，炎症被认为是肺气肿发病机制的一个因素。我们研究了细胞因子浓度（白细胞介素（IL）-1β、IL-1 受体拮抗剂（IL-1RA）、IL-2、IL-4、IL-6、IL-10、IL-17A、肿瘤坏死因子-α（TNFα）、干扰素-γ（IFNγ）、可溶性 CD14（sCD14）和 sCD163）是否与 PLWH 的放射性肺气肿独立相关。
方法
我们纳入了来自哥本哈根 HIV 感染合并症（COCOMO）研究的 PLWH，排除乙型和丙型肝炎合并感染，且有血浆样本和胸部计算机断层扫描（CT）扫描结果。肺气肿伴微量肺气肿定义为-950 豪斯菲尔德单位（Houndsfield Unit）以下低衰减区的百分比（%LAA-950），截断值为 5%。细胞因子浓度通过 ELISA 或 Luminex 免疫测定法测量。细胞因子浓度升高定义为高于第 75 百分位数。
结果
在 783 例 PLWH 中，147 例（18.8%）有肺气肿。PLWH 主要为男性（86.0%），743 例（94.9%）病毒载量不可检测。有肺气肿的 PLWH 其 TNFα 浓度更高（中位数（IQR）：8.2（6.4-9.8）与 7.1（5.7-8.6）pg/ml，p<0.001）、IL-1β（0.21（0.1-0.4）与 0.17（0.1-0.3）pg/ml，p=0.004）和 IL-6（3.6（2.6-4.9）与 3.1（2.0-4.3）pg/ml，p=0.023）。在调整年龄、性别、种族、吸烟状况、BMI 和 CD4 最低点后，TNFα（调整后的优势比（aOR）：1.78 [95%CI：1.14-2.76]，p=0.011）和 IL-1β（aOR：1.81 [95%CI：1.16-2.81]，p=0.009）与肺气肿独立相关。IL-1β与肺气肿的关联受吸烟的修饰（p 交互作用=0.020），在从不吸烟者中更明显（aOR：4.53 [95%CI：2.05-9.98]，p<0.001）。
结论
两种全身炎症标志物 TNFα 和 IL-1β 与 PLWH 的肺气肿独立相关，可能与肺气肿的发病机制有关。重要的是，IL-1β 的作用似乎是通过与过度吸烟无关的途径介导的。
临床试验注册
clinicaltrials.gov，标识符 NCT02382822。
Zotero 插件