J Biol Chem: Blocking deadly cytokine storms is an important weapon in the treatment of COVID-19.

The !---- killer is not a virus, but an immune responseThe current pandemic is unique, not only because it is caused by a new virus that puts everyone at risk, but also because the scope of the innate immune response is diverse and unpredictableSome are even strong enough to be deadlyIn other areas, it is relatively mildThe study by Sasha Poltorak of the Institute of Biomedical Research at Tufts University has been linked to innate immunityCongenital immunity is a person's innate defense against pathogens that instructs the body's adaptive immune system to produce antibodies against the virusThese antibody reactions can later be used to develop vaccination methodsIn the lab of Nobel laureate Bruce Beutler, I co-authored a paper explaining how the cells that make up the body's innate immune system recognize pathogens and how over-reaction to pathogens in general can be harmful to the hostThis is especially true in patients with COVID-19 who over-respond to the virusCell death -- a sacrificial chess game Poltorak studies inflammatory responses and cell death, which are the two main components of innate responsesMacrophages are white blood cells that use a set of sensors to identify pathogens and produce a protein called cytokine, which triggers inflammation and seeks help from other cells in the innate immune systemIn addition, macrophages indicate adaptive immune systems to understand pathogens and eventually produce antibodiesIn order to survive in the host body, successful pathogens inhibit the inflammatory responseThey alert other parts of the immune system by blocking the ability of macrophages to release cytokinesTo combat the silence of the virus, infected cells commit suicide, or the cells dieAlthough cell death is harmful at the cellular level, cell death at the body level is beneficial because it prevents the proliferation of pathogensBetween 1347 and 1351, for example, the Black Death claimed half of the lives of the European populationThe black death pathogen can cause people's white blood cells to lose function, or silence them, and multiply in white blood cells, eventually leading to individual deathIn rodents, however, the results of infection are differentOnly infected macrophages die, limiting the spread of pathogens in rodents and allowing them to surviveThe 'silent' response to plague is very different from the strong response to the SARS-CoV-2 virus that causes COVID-19This suggests that maintaining a balance of innate reactions is critical to the survival of PATIENTs with COVID-19Beneath the path of cytokine storms is how the immune system's over-reaction can harm the body's resistance to infectionSome of the inflammatory proteins, known as chemofactors, warn other immune cells -- such as neutrophils, a professional microbial killer -- that gather at the site of infection and can be the first to reach and digest pathogensOther cytokines -- such as leukocyte interleukin 1b, leukocyte interleukin 6, and tumor necrosis factor -- guide neutrophils from blood vessels into infected tissueThese cytokines can increase the heartbeat, raise body temperature, trigger blood clots, trap pathogens, stimulate neurons in the brain to regulate body temperature, fever, weight loss, and other physiological responses that have evolved to kill the virusWhen the production of these cytokines is out of control, immunologists describe them as 'cytokine storms'During cytokine storms, blood vessels further dilate (vascularization), resulting in low blood pressure and extensive vascular damageThe storm triggers a large number of white blood cells to enter the lungs, which in turn stimulates more immune cells, targeting and killing infected cellsThe result of this battle was a pile of fluids and dead cells, and the subsequent organ failureCytokine storms are at the heart of COVID-19 pathology and have devastating consequences for the hostWhen cells cannot stop the inflammatory response, cytokines are produced to overactivity of macrophagesActivated macrophages destroy stem cells in the bone marrow, leading to anemia Elevated leukocyte interleukin 1b can lead to fever and organ failure Too many tumor necrosis factors can cause a large number of deaths of endovascular wall cells, which can lead to blood vessel condensation To some extent, the storm became unstoppable and irreversible One strategy for treating COVID, which breaks the cytokine storm, is to be based in part on breaking the vicious cycle of cytokine storms This can be used to block the storm's main medium, such as IL6 or its receptors, which are present in all cells of the body FDA-approved antibody drugs such as Remicade or Humira or soluble receptors such as Enbrel (originally developed by Bruce Beutler) can inhibit tumor necrosis, which binds to tumor necrosis and prevents it from triggering inflammation The global market for tumor necrosis factor inhibitors is $22 billion Drugs that block multiple cytokines are currently undergoing clinical trials to test whether they are effective in stopping the vicious cycle of COVID-19