tetano
Editor, Senior Moderator
iScience
. 2020 Dec 7;101896.
doi: 10.1016/j.isci.2020.101896. Online ahead of print.
Transcriptional response modules characterise IL-1β and IL-6 activity in COVID-19
Lucy Ck Bell[SUP] 1 2 [/SUP], Cem Meydan[SUP] 3 [/SUP], Jacob Kim[SUP] 4 5 [/SUP], Jonathan Foox[SUP] 3 6 [/SUP], Daniel Butler[SUP] 3 6 [/SUP], Christopher E Mason[SUP] 3 6 7 8 [/SUP], Sagi D Shapira[SUP] 4 5 [/SUP], Mahdad Noursadeghi[SUP] 1 2 [/SUP], Gabriele Pollara[SUP] 1 9 [/SUP]
Affiliations
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.
Keywords: COVID-19; IL-1β; IL-6; modules; transcriptomics.
. 2020 Dec 7;101896.
doi: 10.1016/j.isci.2020.101896. Online ahead of print.
Transcriptional response modules characterise IL-1β and IL-6 activity in COVID-19
Lucy Ck Bell[SUP] 1 2 [/SUP], Cem Meydan[SUP] 3 [/SUP], Jacob Kim[SUP] 4 5 [/SUP], Jonathan Foox[SUP] 3 6 [/SUP], Daniel Butler[SUP] 3 6 [/SUP], Christopher E Mason[SUP] 3 6 7 8 [/SUP], Sagi D Shapira[SUP] 4 5 [/SUP], Mahdad Noursadeghi[SUP] 1 2 [/SUP], Gabriele Pollara[SUP] 1 9 [/SUP]
Affiliations
- PMID: 33319166
- PMCID: PMC7721347
- DOI: 10.1016/j.isci.2020.101896
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.
Keywords: COVID-19; IL-1β; IL-6; modules; transcriptomics.