Rebekka F Thudium1, Andreas D Knudsen1,2, Jakob Hjorth Von Stemann3, Malene Hove-Skovsgaard1, Hedda Hoel4, Amanda Mocroft5, Joanne Reekie6, Andreas Ronit7, Jan Gerstoft1, Jørgen Vestbo8, Marius Trøseid4, Álvaro H Borges9, Sisse R Ostrowski3, Susanne D Nielsen1. 1. Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 2. Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 3. Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 4. Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway. 5. Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, United Kingdom. 6. Centre for Health and Infectious Diseases (CHIP), Department of Infectious Diseases, Section 2100, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 7. Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark. 8. Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, United Kingdom. 9. Department of Infectious Diseases Immunology, Statens Serum Institut, Copenhagen, Denmark.
Abstract
BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with an increased risk of chronic pulmonary diseases. We compared cytokine concentrations (interleukin 6 [IL-6], interleukin 1β, 2, 4, 10, and 17A, tumor necrosis factor α, interferon γ, soluble CD14 [sCD14] and soluble CD163 [sCD163]) in people with HIV (PWH) and uninfected controls and investigated whether elevated cytokine concentrations were independently associated with lung function indices in PWH. METHODS: We performed spirometry and measured cytokine concentrations by Luminex immunoassays or enzyme-linked immunoassay in 951 PWH and 79 uninfected controls from the Copenhagen Comorbidity in HIV Infection study. Regression analyses were used to explore associations between elevated cytokine concentrations and lung function indices. RESULTS: PWH were predominantly male (84.6%) and 94.2% had undetectable viral replication. In PWH, elevated IL-6 was associated with lower forced expiratory volume in 1 second (-212 mL [95% confidence interval, -308 to -116 mL]), lower forced vital capacity (-208 mL [-322 to -93 mL]), and airflow limitation (aOR, 2.62 [1.58-4.36]) (all P < .001) in models adjusted for age, sex, ethnicity, smoking status, body mass index, and CD4 T-cell nadir. The association between IL-6 and dynamic lung function was modified by smoking (P for interaction = .005). CONCLUSION: IL-6 levels were elevated and independently associated with low dynamic lung function and airflow limitation in well-treated PWH, suggesting that systemic inflammation may contribute to the pathogenesis of chronic pulmonary diseases.
BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with an increased risk of chronic pulmonary diseases. We compared cytokine concentrations (interleukin 6 [IL-6], interleukin 1β, 2, 4, 10, and 17A, tumor necrosis factor α, interferon γ, soluble CD14 [sCD14] and soluble CD163 [sCD163]) in people with HIV (PWH) and uninfected controls and investigated whether elevated cytokine concentrations were independently associated with lung function indices in PWH. METHODS: We performed spirometry and measured cytokine concentrations by Luminex immunoassays or enzyme-linked immunoassay in 951 PWH and 79 uninfected controls from the Copenhagen Comorbidity in HIV Infection study. Regression analyses were used to explore associations between elevated cytokine concentrations and lung function indices. RESULTS: PWH were predominantly male (84.6%) and 94.2% had undetectable viral replication. In PWH, elevated IL-6 was associated with lower forced expiratory volume in 1 second (-212 mL [95% confidence interval, -308 to -116 mL]), lower forced vital capacity (-208 mL [-322 to -93 mL]), and airflow limitation (aOR, 2.62 [1.58-4.36]) (all P < .001) in models adjusted for age, sex, ethnicity, smoking status, body mass index, and CD4 T-cell nadir. The association between IL-6 and dynamic lung function was modified by smoking (P for interaction = .005). CONCLUSION: IL-6 levels were elevated and independently associated with low dynamic lung function and airflow limitation in well-treated PWH, suggesting that systemic inflammation may contribute to the pathogenesis of chronic pulmonary diseases.
Authors: Rebekka F Thudium; Hedda Ringheim; Andreas Ronit; Hedda Hoel; Thomas Benfield; Amanda Mocroft; Jan Gerstoft; Marius Trøseid; Álvaro H Borges; Sisse R Ostrowski; Jørgen Vestbo; Susanne D Nielsen Journal: Front Immunol Date: 2021-04-14 Impact factor: 7.561