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Transcriptional response modules characterize IL-1β and IL-6 activity in COVID-19.


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.

SUBMITTER: Bell LCK 

PROVIDER: S-EPMC7721347 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Transcriptional response modules characterize IL-1β and IL-6 activity in COVID-19.

Bell Lucy C K LCK   Meydan Cem C   Kim Jacob J   Foox Jonathan J   Butler Daniel D   Mason Christopher E CE   Shapira Sagi D SD   Noursadeghi Mahdad M   Pollara Gabriele G  

iScience 20201207 1


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 <i>in vivo</i> 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 juveni  ...[more]

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