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Hindi Targeting of the NLRP3 Inflammasome for Early COVID-19
*Corresponding Author:
Copyright: © 2021 . This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Following entry and replication of Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) into ACE2 expressing cells, the infected cells undergo lysis releasing more viruses but also cell contents. In the lung, constitutive cytokines such as IL-1α are released together with other cell contents. A cascade of inflammatory cytokines ensues, including chemokines and IL-1β, triggering both local as well as systemic inflammation. This cascade of inflammatory cytokines in patients with COVID-19 is termed “Cytokine Release Syndrome” (CRS), and is associated with poor outcomes and death. Many studies reveal that blocking IL-1 activities in COVID-19 patients reduces disease severity and deaths. Here we report highly significant circulating levels of IL-1β, IL-1 Receptor antagonist, IL-6, TNFα, IL-10 and soluble urokinase plasminogen activator receptor in COVID-19 patients with mild or no symptoms. We also report that in circulating myeloid cells from the same patients, there is increased expression of the NOD-, LRR- and pyrin domain containing 3 (NLRP3) early in the infection. We observed increased NLRP3 gene expression in myeloid cells correlated with IL-1β gene expression and also with elevated circulating IL-1β levels. We conclude that early in SARS-CoV-2 infection, NLRP3 activation takes place and initiates the CRS. Thus, NLRP3 is a target to reduce the organ damage of inflammatory cytokines of the CRS.
