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

被引：28

作者：

Bell, Lucy C. K. ^{[1
,2
]}

Meydan, Cem ^{[3
]}

Kim, Jacob ^{[4
,5
]}

Foox, Jonathan ^{[3
,6
]}

Butler, Daniel ^{[3
,6
]}

Mason, Christopher E. ^{[3
,6
,7
,8
]}

Shapira, Sagi D. ^{[4
,5
]}

Noursadeghi, Mahdad ^{[1
,2
]}

Pollara, Gabriele ^{[1
,9
]}

机构：

[1] UCL, Div Infect & Immun, Cruciform Bldg,Gower St, London WC1 6BT, England

[2] Univ Coll London Hosp NHS Trust, Hosp Trop Dis, London, England

[3] Weill Cornell Med, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY USA

[4] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA

[5] Columbia Univ, Dept Syst Biol, New York, NY USA

[6] Weill Cornell Med, Dept Physiol & Biophys, New York, NY USA

[7] Weill Cornell Med, WorldQuant Initiat Quantitat Predict, New York, NY USA

[8] Weill Cornell Med, Feil Family Brain & Mind Res Inst, New York, NY USA

[9] Royal Free London NHS Trust, Dept Infect, London, England

来源：

ISCIENCE | 2021年 / 24卷 / 01期

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

TOCILIZUMAB;

D O I：

10.1016/j.isci.2020.101896

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Dysregulated IL-1 beta 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-1 beta and IL-6 in COVID-19. We show that the expression of IL-1 beta 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-1 beta 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-1 beta 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.

引用

页数：21

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