Cytokine Storm as a Cellular Response to dsDNA Breaks: A New Proposal.
COVID-19
Cytokine storm
apoptosis
copper
dsDNA breaks
free radicals
inflammation
resveratrol
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
29
10
2020
accepted:
07
01
2021
entrez:
18
2
2021
pubmed:
19
2
2021
medline:
27
2
2021
Statut:
epublish
Résumé
Pathogenesis of cytokine storm is poorly understood. In this article we propose a new mechanism and suggest innovative therapeutic avenues for its prevention. We have reported that particles of cell-free chromatin (cfCh) that are released from the billions of cells that die in the body everyday can illegitimately integrate into genomes of healthy cells to trigger dsDNA breaks. The latter leads to apoptosis and/or intense activation of inflammatory cytokines in the affected cells. We hypothesise that a similar phenomenon of dsDNA breaks and inflammation is involved in cytokine storm. The abundant cfCh particles that are released from dying host cells following viral/microbial invasion initiate a cascading effect of more cell death resulting in a vicious cycle of further DNA damage, apoptosis and hyper-inflammation which culminate in cytokine storm. We propose that this unrelenting vicious cycle of cellular DNA damage and cytokine storm may be the underlying cause of high mortality from severe COVID-19. We discuss results of our preclinical studies wherein we have shown that endotoxin induced cytokine storm in mice can be reversed by three different agents that have the ability to inactivate cfCh. These agents may be worthy of investigation in clinical trials to reduce mortality from COVID-19.
Identifiants
pubmed: 33597956
doi: 10.3389/fimmu.2021.622738
pmc: PMC7882731
doi:
Substances chimiques
Endotoxins
0
Free Radicals
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
622738Informations de copyright
Copyright © 2021 Shabrish and Mittra.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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