白细胞介素-1β 和白细胞介素-10 水平升高与治疗良好的人类免疫缺陷病毒感染者肺功能下降更快相关。

Elevated Levels of Interleukin-1β and Interleukin-10 Are Associated With Faster Lung Function Decline in People With Well-Treated Human Immunodeficiency Virus.

机构信息

Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark.

Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.

出版信息

J Infect Dis. 2023 Oct 18;228(8):1080-1088. doi: 10.1093/infdis/jiad233.

Abstract

BACKGROUND

People with human immunodeficiency virus (PWH) have an increased risk of chronic lung diseases and chronic inflammation. We aimed to investigate if inflammatory markers and monocyte activation are associated with faster lung function decline in PWH.

METHODS

We included 655 PWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study. Eligible participants were aged ≥25 years and had 2 spirometries separated by >2 years. Inflammatory markers (interleukin [IL]-1β, IL-2, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ) were measured at baseline by Luminex, and soluble CD14 and soluble CD163 by enzyme-linked immunosorbent assay. Using linear mixed models, we investigated whether elevated cytokine levels were associated with faster lung function decline.

RESULTS

The majority of PWH were males (85.2%) with undetectable viral replication (95.3%). We found a faster decline in forced expiratory volume in 1 second (FEV1) in PWH with elevated IL-1β and IL-10, with an additional decline of 10.3 mL/year (95% confidence interval [CI], 2.1-18.6; P = .014) and 10.0 mL/year (95% CI, 1.8-18.2; P = .017), respectively. We found no interaction between smoking and IL-1β or IL-10 on FEV1 decline.

CONCLUSIONS

Elevated IL-1β and IL-10 were independently associated with faster lung function decline in PWH, suggesting that dysregulated systemic inflammation may play a role in the pathogenesis of chronic lung diseases.

摘要

背景

人类免疫缺陷病毒(HIV)感染者患慢性肺部疾病和慢性炎症的风险增加。我们旨在研究炎症标志物和单核细胞活化是否与 HIV 感染者的肺功能下降速度加快有关。

方法

我们纳入了来自哥本哈根合并感染(COCOMO)研究的 655 名 HIV 感染者。合格的参与者年龄≥25 岁,且两次肺功能检查相隔>2 年。基线时通过 Luminex 测量炎症标志物(白细胞介素[IL]-1β、IL-2、IL-6、IL-10、肿瘤坏死因子-α和干扰素-γ),通过酶联免疫吸附试验测量可溶性 CD14 和可溶性 CD163。我们采用线性混合模型研究了细胞因子水平升高是否与肺功能下降速度加快有关。

结果

大多数 HIV 感染者为男性(85.2%),病毒载量不可检测(95.3%)。我们发现,IL-1β和 IL-10 升高的 HIV 感染者的 1 秒用力呼气量(FEV1)下降速度更快,每年分别下降 10.3 毫升(95%置信区间[CI],2.1-18.6;P=0.014)和 10.0 毫升(95%CI,1.8-18.2;P=0.017)。我们未发现吸烟与 IL-1β或 IL-10 对 FEV1 下降的相互作用。

结论

IL-1β 和 IL-10 升高与 HIV 感染者的肺功能下降速度加快独立相关,提示系统性炎症失调可能在慢性肺部疾病的发病机制中起作用。

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