Bell, LCK;
Meydan, C;
Kim, J;
Foox, J;
Butler, D;
Mason, CE;
Shapira, SD;
... Pollara, G; + view all
(2020)
Transcriptional response modules characterise IL-1β and IL-6 activity in COVID-19.
iScience
, Article 101896. 10.1016/j.isci.2020.101896.
(In press).
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Abstract
Dysregulated IL-1β and IL-6 responses have been implicated in the pathogenesis of severe Coronavirus Disease 2019 (COVID-19). Innovative approaches for evaluating the biological activity of these cytokines in vivo are urgently needed to complement clinical trials of therapeutic targeting of IL-1β and IL-6 in COVID-19. We show that the expression of IL-1β or IL-6 inducible transcriptional signatures (modules) reflects the bioactivity of these cytokines in immunopathology modelled by juvenile idiopathic arthritis (JIA) and rheumatoid arthritis. In COVID-19, elevated expression of IL-1β and IL-6 response modules, but not the cytokine transcripts themselves, is a feature of infection in the nasopharynx and blood, but is not associated with severity of COVID-19 disease, length of stay or mortality. We propose that IL-1β and IL-6 transcriptional response modules provide a dynamic readout of functional cytokine activity in vivo, aiding quantification of the biological effects of immunomodulatory therapies in COVID-19.
Type: | Article |
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Title: | Transcriptional response modules characterise IL-1β and IL-6 activity in COVID-19 |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1016/j.isci.2020.101896 |
Publisher version: | https://doi.org/10.1016/j.isci.2020.101896 |
Language: | English |
Additional information: | This is an Open Access article published under a Creative Commons Attribution 4.0 International (CC BY 4.0) licence (https://creativecommons.org/licenses/by/4.0/). |
Keywords: | COVID-19, transcriptomics, modules, IL-1β, IL-6 |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
URI: | https://discovery.ucl.ac.uk/id/eprint/10117431 |
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