Connect with us


Mechanism of IL-6 expression in SARS-CoV-2 infected peripheral monocyte-derived macrophages




In a recent study posted on Research Square* Preprint server. Scientific ReportsResearchers investigated the detailed mechanism of’Cytokine storm‘This induces acute respiratory distress syndrome (ARDS) and often leads to the death of patients with severe coronavirus disease 2019 (COVID-19).

study: Enhanced antibody dependence of IL-6 production by SARS-CoV-2 nucleocapsid protein.. Image Credit: Maryna Olyak / Shutterstock

Previous studies have shown the involvement of cytokines such as interleukin (IL) -6 in ARDS by SARS-CoV-2 infection with severe acute respiratory syndrome. In addition, studies have shown the presence of IL-6-producing CD14 + CD16 + monocytes in the peripheral blood of COVID-19 patients in the intensive care unit compared to COVID-19 patients who do not require hospitalization. ..

Monocytes are often the first cells of the immune system to come into contact with viral pathogens, including SARS-CoV-2. However, the detailed mechanism of IL-6 expression in SARS-CoV-2 infected peripheral monocyte-derived macrophages (MDM) is unknown.

About research

In this study, researchers added frozen / thawed lysates of SARS-CoV-2 infected cells to cultured macrophages (MDM) or pluripotent bone marrow cells to mimic SARS-CoV-2 infection in the alveoli. And then these cells secreted IL-6. They studied the underlying mechanisms that regulate IL-6 expression in SARS-CoV-2 infected peripheral monocyte-derived macrophages (MDM). They also showed that anti-nucleocapsid (N) antibodies enhance the induction of IL-6 via nucleocapsid (N) proteins.

Survey results

Transmembrane serine protease 2 (TMPRSS2) / VeroE6 cells infected with SARS-CoV-2 while investigating the effects of SARS-CoV-2 infected cells on MDM (as a model of SARS-CoV-2 infection in the alveolar) The lysate was added to MDM along with SARS-CoV-2.

Despite the fact that SARS-CoV-2 RNA levels decreased over time, the authors found that IL-6 in the supernatant of MDM incubated with SARS-CoV-2 infected cytolysis. We focused on increasing levels, but not for non-infected cells. Lysate. Interestingly, three different strains of SARS-CoV-2 isolates were able to induce IL-6 production by MDM.

Testing myelomonocyte leukemia cells (K-ML2) cells as an alternative to MD, the authors found that SARS-CoV-2 infected cell lysates induce IL-6 production from K-ML2 cells and SARS- We noted that it suggests a specific component of CoV-2. -Infected cells stimulated MDM and K-ML2 cells to produce IL-6.

By screening for SARS-CoV-2 protein expression plasmid transfected into a derivative of human fetal kidney 293 cells containing SV40 T antigen (293T cells), SARS-CoV-2N protein containing recombinant N protein produces IL-6. It was found to be more efficient than the SARS_CoV-2 spike (S) protein. In addition, using a plasmid encoding a shortened version of the N protein, the authors were able to identify that the C-terminal domain (CTD) of the N protein is responsible for IL-6-induced activity.

In both culture supernatants of granulocyte macrophage colony stimulating factor (GM-CSF) stimulating factor and macrophage colony stimulating factor (M-CSF) stimulated MDM, after 2 days of N protein stimulation, the assay results show elevated levels of multiple cytokines. Was shown. All these cytokines, including IL-6, IL-8, tumor necrosis factor (TNF-α), macrophage inflammatory protein-1 beta (MIP-1β), pentraxin-3, thymic stromal phosphopoietin (TSLP), Rise during severe COVID-19.

In GM-CSF-stimulated MDM, an increase in N-protein-induced increase in IP-10, a predictor of severe disease of COVID-19, was observed, and even if MDM was not productive, cytokines in COVID-19 patients were observed. Infection with SARS-CoV-2 indicates that it can be a source.

Transfection of K-ML2 cells containing N protein with serially diluted patient sera from actual SARS-CoV-2 patients enhanced IL-6 production, although 0.01-10% of COVID-19 patient sera enhanced IL-6 production. Serum from 5 healthy donors does not enhance IL-6 production.

In addition, when researchers evaluated 203 serum samples from mild, moderate, and severe COVID-19 cases, the serum of severe patients induced significantly more IL-6 than other patients. Was observed. Similarly, anti-N antibody levels also increased.


This study showed that SARS-CoV-2 infected epithelial cells induce IL-6 production via bystander macrophages or bone marrow cells (due to the presence of the SARS-CoV-2 N protein). therefore, COVID19 Symptoms It may worsen rapidly 5 to 8 days after the onset of symptoms, and anti-N antibodies enhance this phenomenon.

The results showed that the proposed mechanism of antibody-dependent enhancement (ADE) of IL-6 production from macrophages could occur without actual productive SARS-CoV-2 infection.Therefore, this study provided relatively little evidence. Effectiveness of An all-virus-based COVID-19 vaccine that is more inactivated than the widely used messenger ribonucleic acid (mRNA) -based vaccines such as the Moderna vaccine.

For COVID-19 treatment, steroids and anti-IL-6 receptor antibodies are recommended to suppress the excessive immune response. Five anti-N antibodies, including N1, N4, N5, N9, and N12, may serve as a new therapeutic strategy for COVID-19, which will be treated in future studies based on IL-6 suppression. Only possible if is established.

*Important Notices

Research Square preprints publish unpeer-reviewed preliminary scientific reports that are considered definitive, guide clinical / health-related behaviors, and are treated as established information. Should not be.




The mention sources can contact us to remove/changing this article

What Are The Main Benefits Of Comparing Car Insurance Quotes Online

LOS ANGELES, CA / ACCESSWIRE / June 24, 2020, / Compare-autoinsurance.Org has launched a new blog post that presents the main benefits of comparing multiple car insurance quotes. For more info and free online quotes, please visit https://compare-autoinsurance.Org/the-advantages-of-comparing-prices-with-car-insurance-quotes-online/ The modern society has numerous technological advantages. One important advantage is the speed at which information is sent and received. With the help of the internet, the shopping habits of many persons have drastically changed. The car insurance industry hasn't remained untouched by these changes. On the internet, drivers can compare insurance prices and find out which sellers have the best offers. View photos The advantages of comparing online car insurance quotes are the following: Online quotes can be obtained from anywhere and at any time. Unlike physical insurance agencies, websites don't have a specific schedule and they are available at any time. Drivers that have busy working schedules, can compare quotes from anywhere and at any time, even at midnight. Multiple choices. Almost all insurance providers, no matter if they are well-known brands or just local insurers, have an online presence. Online quotes will allow policyholders the chance to discover multiple insurance companies and check their prices. Drivers are no longer required to get quotes from just a few known insurance companies. Also, local and regional insurers can provide lower insurance rates for the same services. Accurate insurance estimates. Online quotes can only be accurate if the customers provide accurate and real info about their car models and driving history. Lying about past driving incidents can make the price estimates to be lower, but when dealing with an insurance company lying to them is useless. Usually, insurance companies will do research about a potential customer before granting him coverage. Online quotes can be sorted easily. Although drivers are recommended to not choose a policy just based on its price, drivers can easily sort quotes by insurance price. Using brokerage websites will allow drivers to get quotes from multiple insurers, thus making the comparison faster and easier. For additional info, money-saving tips, and free car insurance quotes, visit https://compare-autoinsurance.Org/ Compare-autoinsurance.Org is an online provider of life, home, health, and auto insurance quotes. This website is unique because it does not simply stick to one kind of insurance provider, but brings the clients the best deals from many different online insurance carriers. In this way, clients have access to offers from multiple carriers all in one place: this website. On this site, customers have access to quotes for insurance plans from various agencies, such as local or nationwide agencies, brand names insurance companies, etc. "Online quotes can easily help drivers obtain better car insurance deals. All they have to do is to complete an online form with accurate and real info, then compare prices", said Russell Rabichev, Marketing Director of Internet Marketing Company. CONTACT: Company Name: Internet Marketing CompanyPerson for contact Name: Gurgu CPhone Number: (818) 359-3898Email: [email protected]: https://compare-autoinsurance.Org/ SOURCE: Compare-autoinsurance.Org View source version on accesswire.Com:https://www.Accesswire.Com/595055/What-Are-The-Main-Benefits-Of-Comparing-Car-Insurance-Quotes-Online View photos


to request, modification Contact us at Here or [email protected]