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

Author:

Thudium Rebekka F1,Arentoft Nicoline S1ORCID,Hoel Hedda2,Afzal Shoaib34ORCID,von Stemann Jakob H5,Forman Julie L6ORCID,Wilcke Jon T7,Benfield Thomas48ORCID,Trøseid Marius2,Borges Álvaro H9,Ostrowski Sisse R45,Vestbo Jørgen10,Kunisaki Ken M1112,Jensen Jens-Ulrik S78,Nielsen Susanne D14ORCID

Affiliation:

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

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

3. The Copenhagen General Population Study, Department of Clinical Biochemistry, Copenhagen University Hospital—Herlev and Gentofte , Herlev

4. Department of Clinical Medicine, Faculty of Health and Medical Sciences

5. Department of Clinical Immunology, Rigshospitalet

6. Department of Public Health, Section of Biostatistics, University of Copenhagen

7. Department of Respiratory Medicine, Herlev-Gentofte Hospital , Gentofte

8. Department of Infectious Diseases, Copenhagen University Hospital—Amager and Hvidovre Hospital , Hvidovre

9. Department of Infectious Diseases Immunology, Statens Serum Institut , Copenhagen , Denmark

10. Division of Infection, Immunity and Respiratory Medicine, University of Manchester , Manchester , United Kingdom

11. Minneapolis Veterans Affairs Health Care System , Minneapolis, Minnesota, USA

12. Department of Medicine, University of Minnesota , Minneapolis, Minnesota, USA

Abstract

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.

Funder

Rigshospitalet Research Council

Novo Nordisk Foundation

Gilead Sciences

National Institute for Health and Care Research Manchester Biomedical Research Center

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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