iScience (Oct 2024)
Association of inflammatory cytokines with lung function, chronic lung diseases, and COVID-19
- Marina O. Rontogianni,
- Dipender Gill,
- Emmanouil Bouras,
- Alexandros-Georgios Asimakopoulos,
- Ioanna Tzoulaki,
- Ville Karhunen,
- Terho Lehtimäki,
- Olli Raitakari,
- Matthias Wielscher,
- Veikko Salomaa,
- Sirpa Jalkanen,
- Marko Salmi,
- Markku Timonen,
- James Yarmolinsky,
- Jing Chen,
- Martin D. Tobin,
- Abril G. Izquierdo,
- Karl-Heinz Herzig,
- Anne E. Ioannides,
- Marjo-Riitta Jarvelin,
- Abbas Dehghan,
- Konstantinos K. Tsilidis
Affiliations
- Marina O. Rontogianni
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
- Dipender Gill
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Emmanouil Bouras
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
- Alexandros-Georgios Asimakopoulos
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
- Ioanna Tzoulaki
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Ville Karhunen
- Research Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland; Research Unit of Mathematical Sciences, University of Oulu, Oulu, Finland
- Terho Lehtimäki
- Department of Clinical Chemistry, Faculty of Medicine & Health Technology, Tampere University, Tampere, Finland; Finnish Cardiovascular Research Center Tampere, Faculty of Medicine & Health Technology, Tampere University, Tampere, Finland; Fimlab Laboratories, Tampere, Finland
- Olli Raitakari
- Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
- Matthias Wielscher
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Veikko Salomaa
- Finnish Institute for Health and Welfare, Helsinki, Finland
- Sirpa Jalkanen
- MediCity Research Laboratory, University of Turku, Turku, Finland; Institute of Biomedicine, University of Turku, Turku, Finland; InFLAMES Fiagship, University of Turku, Turku, Finland
- Marko Salmi
- MediCity Research Laboratory, University of Turku, Turku, Finland; Institute of Biomedicine, University of Turku, Turku, Finland; InFLAMES Fiagship, University of Turku, Turku, Finland
- Markku Timonen
- Research Unit of Population Health, University of Oulu, Oulu, Finland; Medical Research Center (MRC) and University Hospital, Oulu, Finland
- James Yarmolinsky
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- Jing Chen
- Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK
- Martin D. Tobin
- Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK; National Institute for Health Research, Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, UK
- Abril G. Izquierdo
- Department of Health Sciences, University of Leicester, Leicester, UK
- Karl-Heinz Herzig
- Medical Research Center (MRC) and University Hospital, Oulu, Finland; Research Unit of Biomedicine and Internal Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland; Pediatric Gastroenterology and Metabolic Diseases, Pediatric Institute, Poznan University of Medical Sciences, Poznan, Poland
- Anne E. Ioannides
- Department of Primary Care and Public Health, School of Public Health, Imperial College London, White City Campus, London, UK
- Marjo-Riitta Jarvelin
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; Research Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland; Unit of Primary Care, Oulu University Hospital, Oulu, Finland; Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, UK
- Abbas Dehghan
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; UK Dementia Research Institute at Imperial College London, London, UK
- Konstantinos K. Tsilidis
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; Corresponding author
- Journal volume & issue
-
Vol. 27,
no. 10
p. 110704
Abstract
Summary: We investigated the effects of 35 inflammatory cytokines on respiratory outcomes, including COVID-19, asthma (atopic and non-atopic), chronic obstructive pulmonary disease (COPD), and pulmonary function indices, using Mendelian randomization and colocalization analyses. The emerging associations were further explored using observational analyses in the UK Biobank. We found an inverse association between genetically predicted macrophage colony stimulating factor (MCSF), soluble intercellular adhesion molecule-1 (sICAM), and soluble vascular cell adhesion molecule-1 with risk of COVID-19 outcomes. sICAM was positively associated with atopic asthma risk, whereas tumor necrosis factor-alfa showed an inverse association. A positive association was shown between interleukin-18 and COPD risk (replicated in observational analysis), whereas an inverse association was shown for interleukin-1 receptor antagonist (IL-1ra). IL-1ra and monocyte chemotactic protein-3 were positively associated with lung function indices, whereas inverse associations were shown for MCSF and interleukin-18 (replicated in observational analysis). Our results point to these cytokines as potential pharmacological targets for respiratory traits.
