Transcriptional response modules characterise IL-1β and IL-6 activity in COVID-19
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.
| Errataetall: |
UpdateIn: iScience. 2021 Jan 22;24(1):101896. - PMID 33319166 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2020 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2020) vom: 03. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bell, Lucy Ck [VerfasserIn] |
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Date Revised 10.11.2023 published: Electronic UpdateIn: iScience. 2021 Jan 22;24(1):101896. - PMID 33319166 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2020.07.22.202275 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM318654016 |
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| 500 | |a UpdateIn: iScience. 2021 Jan 22;24(1):101896. - PMID 33319166 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Preprint | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a IL-1β | |
| 650 | 4 | |a IL-6 | |
| 650 | 4 | |a modules | |
| 650 | 4 | |a transcriptomics | |
| 700 | 1 | |a Meydan, Cem |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Jacob |e verfasserin |4 aut | |
| 700 | 1 | |a Foox, Jonathan |e verfasserin |4 aut | |
| 700 | 1 | |a Butler, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Mason, Christopher E |e verfasserin |4 aut | |
| 700 | 1 | |a Shapira, Sagi D |e verfasserin |4 aut | |
| 700 | 1 | |a Noursadeghi, Mahdad |e verfasserin |4 aut | |
| 700 | 1 | |a Pollara, Gabriele |e verfasserin |4 aut | |
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