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

doi:10.1016/j.isci.2024.110704

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^*

^*Tämän työn vastaava kirjoittaja

Tutkimustuotos: Artikkeli › Tieteellinen › vertaisarvioitu

1 Sitaatiot (Scopus)

12 Lataukset (Pure)

Abstrakti

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.

Alkuperäiskieli	Englanti
Artikkeli	110704
Sivumäärä	14
Julkaisu	iScience
Vuosikerta	27
Numero	10
DOI - pysyväislinkit	https://doi.org/10.1016/j.isci.2024.110704
Tila	Julkaistu - 18 lokak. 2024
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Rahoitus

This study is co-financed by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program \u201CCompetitiveness, Entrepreneurship and Innovation (EPAnEK), NSRF 2014-2020 (Project code MIS: O\u03A0\u03A3 5047228).\u201D 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; Yrj\u00F6 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). The authors declare the following competing interests: Salomaa Veikko was funded by the Finnish Foundation for Cardiovascular Research and by the Juho Vainio Foundation. Salomaa Veikko has received an honorarium from Sanofi for consulting and has ongoing research collaboration with Bayer Ltd. (All outside the present study). These companies had no role in study design, data collection and analysis, decision to publish, or preparation of the article. Sirpa Jalkanen, Marko Salmi: Financial support for cytokine analyses has come from the Finnish Academy. Abril Izquierdo and Martin Tobin were supported for the present article by Wellcome Trust grants (WT202849/Z/16/Z, WT225221/Z/22/Z) and the National Institute of Health and Care Research (NIHR) Leicester Biomedical Research Center. Martin Tobin has also received an NIHR Senior Investigator Award and had a funded research collaboration with Orion Pharma (the latter outside the scope of this work). Markku Timonen has received payment for one lecture for Otsuka Pharmaceutical and payment for two lectures for H. Lundbeck A/S. Marjo-Ritta Jarvelin is partly funded by the Medical Research Council (MR/S019669/1). James Yarmolinsky is supported by a Cancer Research UK Population Research Postdoctoral Fellowship (C68933/A28534). The remaining authors have no competing interests to declare.

Rahoittajat	Rahoittajan numero
Tampereen tuberkuloosisäätiö
Paavo Nurmen Säätiö
Signe ja Ane Gyllenbergin Säätiö
Suomen Kulttuurirahasto
National Institute for Health and Care Research
Suomen kliinisen kemian yhdistys
Population Research Postdoctoral Fellowship
Juho Vainion Säätiö
Emil Aaltosen Säätiö
Diabetesliitto
NIHR Leicester Biomedical Research Centre
Sydäntutkimussäätiö
European Regional Development Fund
Yrjö Jahnssonin säätiö
Sigrid Juséliuksen Säätiö
C68933/A28534
Terveyden ja hyvinvoinnin laitos,	54231, 54121, 50621
Terveyden ja hyvinvoinnin laitos,
Oulun yliopisto	65354
Oulun yliopisto
European Research Council	742927
European Research Council
Medical Research Council	MR/S019669/1
Medical Research Council
Socialdepartementet	190/97, 160/97, 23/251/97
Socialdepartementet
Turun yliopistollinen keskussairaala	X51001
Turun yliopistollinen keskussairaala
EDCMET	825762
Horizon 2020	848146, 755320
Horizon 2020
European Union and Greek national funds	OΠΣ 5047228
Oulu University Hospital	2/97, 8/97
Syöpäsäätiö	NFBC1966
Syöpäsäätiö
Research Council of Finland	320297, 322098, 129378, 338395, 256474, 314389, 255381, 141071, 134309, 124282, 126925, 121584, 283115, 117797, 104821, 319060, 330809, 286284
Research Council of Finland
BBSRC: Biotechnology and Biological Sciences Research Council, United Kingdom	MR/S03658X/1, JPI HDHL H2020
BBSRC: Biotechnology and Biological Sciences Research Council, United Kingdom
Wellcome Trust	WT225221/Z/22/Z, WT202849/Z/16/Z
Wellcome Trust
EU H2020	733206, 873749, 633595, 848158

Julkaisufoorumi-taso

Jufo-taso 1

Pääsy asiakirjaan

10.1016/j.isci.2024.110704Lisenssi: CC BY

1-s2.0-S2589004224019291-mainFinal published version, 4,26 MBLisenssi: CC BY

https://urn.fi/URN:NBN:fi:tuni-2024121111001Lisenssi: CC BY

Siteeraa tätä

Rontogianni, M. O., Gill, D., Bouras, E., Asimakopoulos, A. G., Tzoulaki, I., Karhunen, V., Lehtimäki, T., Raitakari, O., Wielscher, M., Salomaa, V., Jalkanen, S., Salmi, M., Timonen, M., Yarmolinsky, J., Chen, J., Tobin, M. D., Izquierdo, A. G., Herzig, K. H., Ioannides, A. E., ... Tsilidis, K. K. (2024). Association of inflammatory cytokines with lung function, chronic lung diseases, and COVID-19. iScience, 27(10), Artikkeli 110704. https://doi.org/10.1016/j.isci.2024.110704

@article{870f3db71a924551b068032758b22bdc,

title = "Association of inflammatory cytokines with lung function, chronic lung diseases, and COVID-19",

abstract = "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.",

keywords = "Association analysis, Disease, Health sciences, Respiratory medicine",

author = "Rontogianni, \{Marina O.\} and Dipender Gill and Emmanouil Bouras and Asimakopoulos, \{Alexandros Georgios\} and Ioanna Tzoulaki and Ville Karhunen and Terho Lehtim{\"a}ki and Olli Raitakari and Matthias Wielscher and Veikko Salomaa and Sirpa Jalkanen and Marko Salmi and Markku Timonen and James Yarmolinsky and Jing Chen and Tobin, \{Martin D.\} and Izquierdo, \{Abril G.\} and Herzig, \{Karl Heinz\} and Ioannides, \{Anne E.\} and Jarvelin, \{Marjo Riitta\} and Abbas Dehghan and Tsilidis, \{Konstantinos K.\}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

month = oct,

day = "18",

doi = "10.1016/j.isci.2024.110704",

language = "English",

volume = "27",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier",

number = "10",

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Rontogianni, MO, Gill, D, Bouras, E, Asimakopoulos, AG, Tzoulaki, I, Karhunen, V, Lehtimäki, T, Raitakari, O, Wielscher, M, Salomaa, V, Jalkanen, S, Salmi, M, Timonen, M, Yarmolinsky, J, Chen, J, Tobin, MD, Izquierdo, AG, Herzig, KH, Ioannides, AE, Jarvelin, MR, Dehghan, A & Tsilidis, KK 2024, 'Association of inflammatory cytokines with lung function, chronic lung diseases, and COVID-19', iScience, Vuosikerta 27, Nro 10, 110704. https://doi.org/10.1016/j.isci.2024.110704

TY - JOUR

T1 - Association of inflammatory cytokines with lung function, chronic lung diseases, and COVID-19

AU - Rontogianni, Marina O.

AU - Gill, Dipender

AU - Bouras, Emmanouil

AU - Asimakopoulos, Alexandros Georgios

AU - Tzoulaki, Ioanna

AU - Karhunen, Ville

AU - Lehtimäki, Terho

AU - Raitakari, Olli

AU - Wielscher, Matthias

AU - Salomaa, Veikko

AU - Jalkanen, Sirpa

AU - Salmi, Marko

AU - Timonen, Markku

AU - Yarmolinsky, James

AU - Chen, Jing

AU - Tobin, Martin D.

AU - Izquierdo, Abril G.

AU - Herzig, Karl Heinz

AU - Ioannides, Anne E.

AU - Jarvelin, Marjo Riitta

AU - Dehghan, Abbas

AU - Tsilidis, Konstantinos K.

PY - 2024/10/18

Y1 - 2024/10/18

N2 - 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.

AB - 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.

KW - Association analysis

KW - Disease

KW - Health sciences

KW - Respiratory medicine

U2 - 10.1016/j.isci.2024.110704

DO - 10.1016/j.isci.2024.110704

M3 - Article

AN - SCOPUS:85207743948

SN - 2589-0042

VL - 27

JO - iScience

JF - iScience

IS - 10

M1 - 110704

ER -

Association of inflammatory cytokines with lung function, chronic lung diseases, and COVID-19

Abstrakti

Rahoitus

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Pääsy asiakirjaan

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