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

Published: July 23, 2020, 7:56 p.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.22.202275v1?rss=1 Authors: Bell, L. C. K., Noursadeghi, M., Pollara, G. Abstract: Dysregulated IL-1 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 and IL-6 in COVID-19. We show that the expression of IL-1 or IL-6 inducible transcriptional signatures (modules) reflects the bioactivity of these cytokines in juvenile idiopathic arthritis (JIA) and rheumatoid arthritis, and discerns the effect of therapeutic cytokine blockade in JIA. In COVID-19, elevated expression of IL-1 and IL-6 response modules, but not these cytokines per se, is a feature of disease both in blood and in affected organs. We propose that IL-1 and IL-6 transcriptional response modules can provide a dynamic readout of the activity of these cytokine pathways in vivo, with potential applications for identifying COVID-19 patients who may benefit from IL-1 or IL-6 blocking therapy, and to aid quantification of the biological effects of these treatments. Copy rights belong to original authors. Visit the link for more info