A1 Refereed original research article in a scientific journal
Association of inflammatory cytokines with lung function, chronic lung diseases and COVID-19
Authors: Rontogianni, Marina O.; Gill, Dipender; Bouras, Emmanouil; Asimakopoulos, Alexandros-Georgios; Tzoulaki, Ioanna; Karhunen, Ville; Lehtimäki, Terho; Raitakari, Olli; Wielscher, Matthias; Salomaa, Veikko; Jalkanen, Sirpa; Salmi, Marko; Timonen, Markku; Yarmolinsky, James; Chen, Jing; Tobin, Martin D.; Izquierdo, Abril G.; Herzig, Karl-Heinz; Ioannides, Anne E.; Jarvelin, Marjo-Riitta; Dehghan, Abbas; Tsilidis, Konstantinos K.
Publisher: Cell Press
Publication year: 2024
Journal: iScience
Journal name in source: iScience
Article number: 110704
Volume: 27
Issue: 10
eISSN: 2589-0042
DOI: https://doi.org/10.1016/j.isci.2024.110704
Web address : https://doi.org/10.1016/j.isci.2024.110704
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/457515026
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 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 tumour 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.
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Funding information in the publication:
This study is co-financed by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program "Competitiveness, Entrepreneurship and Innovation (EPAnEK), NSRF 2014-2020 (Project code MIS: OΠΣ 5047228)". The Young Finns Study has been financially supported by the Academy of Finland: grants 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 255381, 256474, 283115, 319060, 320297, 314389, 338395, 330809, and 104821, 129378 (Salve), 117797 (Gendi), and 141071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research ; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for To Aition); European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation, Finnish Society of Clinical Chemistry and the Cancer Foundation Finland. NFBC1966 31-year follow up that included cytokine measurements received financial support from University of Oulu Grant no. 65354, Oulu University Hospital Grant no. 2/97, 8/97, Ministry of Health and Social Affairs Grant no. 23/251/97, 160/97, 190/97, National Institute for Health and Welfare, Helsinki Grant no. 54121, Regional Institute of Occupational Health, Oulu, Finland Grant no. 50621, 54231. The data generation, curation and manpower were also supported by the following EU H2020 grants: DynaHEALTH (grant no 633595), LifeCycle (733206), LongITools (873749), EarlyCause (848158), EDCMET (825762) and the Medical Research Council, UK: grant number MRC/BBSRC MR/S03658X/1 (JPI HDHL H2020).
