Cytokine Storms | COVID19 Cytokine Storms | Death in COVID19
Cytokines play an important role in the regulation of the immune system. The two types of cytokines, pro-inflammatory and anti-inflammatory cytokines counterbalance the effect during the during microbial infections or any cytokine related diseases. However, in the cytokine storm, there is an enormous release of pro-inflammatory cytokines that may lead to tissue injury, organ failure or death. Usually, cytokines are an integral part of our immune response to the infection, but their swift release in large quantities can cause immediate death. In simple words, viruses turn our immune system against ourselves and start to destroy its own components. Cytokine storms can be caused by a number of infectious agents especially viral respiratory infections such as H5N1 influenza and SARS-CoV. Cytokine storms are also suspected to be the main cause of death in the 1918 “Spanish Flu” pandemic. Deaths occurred more heavily towards people with healthy immune systems, because of their ability to produce stronger immune responses, with dramatic increases in cytokine levels. In the COVID-19 pandemic, some deaths from COVID-19 have been attributable to cytokine storms. Therefore, it is really important to understand the pathogenesis of cytokine storm. Another example of a cytokine storm is seen in acute pancreatitis. Cytokines are integral and implicated in all angles of the cascade resulting in systemic inflammatory response syndrome and multi-organ failure associated with this disease.
Cytokines are a broad category of small proteins that are important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in cellular signaling as immunomodulating agents.
Cytokines include chemokines, interferons, interleukins, and lymphokines. Cytokines are produced by a broad range of cells, including immune cells like macrophages, T lymphocytes, B lymphocytes, mast cells, endothelial cells, fibroblasts, and stromal cells.
Each cytokine has a matching cell-surface receptor. Subsequent cascades of intracellular signaling then alter cell functions. This may include the upregulation or downregulation of several genes and their transcription factors, resulting in the production of other cytokines, an increase in the number of surface receptors for other molecules, or the suppression of their own effect by feedback inhibition. The effect of a particular cytokine on a given cell depends on the cytokine, its extracellular abundance, the presence of the complementary receptor on the cell surface, and downstream signals activation by receptor binding; these last two factors can vary by cell type.
Pro-inflammatory cytokines include interleukin-1, IL-12, and IL-18, tumor necrosis factor-alpha (TNF-α), interferon-gamma, and granulocyte-macrophage colony-stimulating factor. Major anti-inflammatory cytokines include interleukin (IL)-1 receptor antagonist, IL-4, IL-6, IL-10, IL-11, and IL-13.
Experiments are being conducted to find a cure for cytokine storm. Clinical trials are being conducted on the use of anti-inflammatory therapy during the COVID 19 cytokine storm. The anti-inflammatory therapies have potential side effects hence more research is required to confirm the use of these drugs to control cytokine storm.
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