When we fall ill from infections or other medical conditions, our bodies respond with a complex orchestration of immune reactions. Sometimes, this response can go into overdrive and cause more harm than good. Cytokine release syndrome (CRS), also called hypercytokinemia and colloquially known as cytokine storm, is a severe immune response characterized by the uncontrolled and excessive release of cytokines.
Cytokines are small chemical messenger proteins produced by various immune cells that play a large role in cell signaling during an immune response. Cytokines can control cell proliferation, differentiation processes, and ultimately regulate immune and inflammatory responses in the body. The exaggerated immune responses characterized by CRS can lead to a number of serious issues and can prove to be fatal. CRS is typically triggered by infection or immunotherapy treatments, and has gained attention in recent years, especially in wake of the COVID-19 pandemic.
During a cytokine storm, the immune system overreacts, and there is an excessive release of cytokines into the bloodstream. This flood of cytokines leads to a cascade of amplified immune responses that can prove fatal. The positive feedback loop formed by cytokine storm pushes for further immune cell recruitment to sites of injury, which can damage organs, and ultimately lead to death. CRS gained prominence in recent years with the emergence of COVID-19. COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The virus impacts the respiratory tract, often leads to pneumonia and causes acute respiratory distress syndrome (ARDS) in 15% of cases. ARDS is a severe clinical complication triggered by cytokine storm, due to elevated levels of pro inflammatory cytokines, and is ultimately one of the leading causes of death in COVID-19 patients. “Interleukins, such as interleukin-6 (IL-6), interleukin-1 (IL-1), interleukin-17 (IL-17), and tumor necrosis factor-alpha (TNF-α) play a very significant role in lung damage in ARDS patients through the impairments of the respiratory epithelium” (Montazersaheb et al., 2022). Therefore, these cytokines are considered big players in this cytokine storm and have been heavily researched following the eruption of the pandemic as targets for treating ARDS and severe COVID infection.
Interleukin-6 was quickly targeted due to its role in CRS and the availability of an existing FDA approved drug typically used to treat rheumatoid arthritis and juvenile idiopathic arthritis. “If it is possible to block the signal transduction pathway of IL-6, it is expected to become a new method for the treatment of severe COVID-19 patients. Tocilizumab is an IL-6 receptor (IL-6R) blocker that can effectively block the IL-6 signal transduction pathway and thus is likely to become an effective drug for patients with severe COVID-19” (Zhang et al., 2020). As of early 2022 WHO added the monoclonal antibody tocilizumab to its list of prequalified treatments for COVID-19, and by late 2022 the drug was FDA approved for intravenous treatment in hospitalized adults with severe COVID infections. This approval followed the early use authorization in mid 2021.
In addition to COVID-19, cytokine storm plays a massive role in sepsis. Sepsis is a medical condition that occurs when the body’s response to an infection becomes dysregulated, which leads to widespread inflammation. In sepsis, the immune response to the infection becomes uncontrolled and disproportionate, leading to the excessive release of pro inflammatory cytokines. In 2017 it was estimated that there were nearly 50 million cases of sepsis worldwide, with 11 million sepsis related deaths reported (Rudd et al, 2020). The cytokine storm in sepsis leads to several significant effects on the body.
The widespread inflammation can cause endothelial dysfunction, dangerously low blood pressure, and potentially fatal organ dysfunction. The current main treatment of sepsis involves broad spectrum antibiotics to target the infection. However, ongoing research is looking to better understand cytokine storm, in order to find better therapies in hopes of lowering mortality in sepsis.
Here at SBH Sciences we are a world leader in cell-based assays to measure the biological activity of cytokines and growth factors. Some of the assays offered include the aforementioned cytokines IL-6, IL-1, IL-17 and TNFa. We can also collaborate with any entity that is looking for neutralization of cytokines or cytokine receptors, as we are able to determine neutralization capability of antibodies in each of our assays.
We offer an extremely comprehensive list of 330 different bioassays and excel in both development and validation of cell based assays for cytokines. With multiple cell-based disease models, we offer 370 unique human cancer cell lines for your needs. At SBH Sciences we also offer 11 different platforms for biomarker analysis, including but not limited to ELISA, ELLA, Luminex and MSD. We can collaborate with any party and analyze clinical samples as Research Use Only (RUO) or under GLP/CLIA conditions. Our bioassay and biomarker services can help your company to accelerate discovery and development programs for a very competitive price. Take a look at our cell-based assay and biomarker services, our list of currently available cytokine bioassays, and please contact us to discuss your specific needs!
Sources:
Dinarello C. A. (2007). Historical insights into cytokines. European journal of immunology, 37 Suppl 1(Suppl 1), S34–S45. https://doi.org/10.1002/eji.200737772
Montazersaheb, S., Hosseiniyan Khatibi, S. M., Hejazi, M. S., Tarhriz, V., Farjami, A., Ghasemian Sorbeni, F., Farahzadi, R., & Ghasemnejad, T. (2022). COVID-19 infection: an overview on cytokine storm and related interventions. Virology journal, 19(1), 92. https://doi.org/10.1186/s12985-022-01814-1
Zhang, C., Wu, Z., Li, J. W., Zhao, H., & Wang, G. Q. (2020). Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. International journal of antimicrobial agents, 55(5), 105954. https://doi.org/10.1016/j.ijantimicag.2020.105954
https://www.covid19treatmentguidelines.nih.gov/therapies/immunomodulators/interleukin-6-inhibitors/
Rudd, K. E., Johnson, S. C., Agesa, K. M., Shackelford, K. A., Tsoi, D., Kievlan, D. R., Colombara, D. V., Ikuta, K. S., Kissoon, N., Finfer, S., Fleischmann-Struzek, C., Machado, F. R., Reinhart, K. K., Rowan, K., Seymour, C. W., Watson, R. S., West, T. E., Marinho, F., Hay, S. I., Lozano, R., … Naghavi, M. (2020). Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet (London, England), 395(10219), 200–211. https://doi.org/10.1016/S0140-6736(19)32989-7
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