Biology:Cytokine storm

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Short description: Bodily reaction

A cytokine storm, also called cytokine storm syndrome (CSS) or hypercytokinemia, is a physiological reaction in humans and other animals in which the innate immune system causes an uncontrolled and excessive release of pro-inflammatory signaling molecules called cytokines. Normally, cytokines are part of the body's immune response to infection, but their sudden release in large quantities can cause multisystem organ failure and death.[1] Cytokine storms can be caused by a number of infectious and non-infectious etiologies, especially viral respiratory infections such as H5N1 influenza and SARS-CoV.[2][3] Other causative agents include the Epstein-Barr virus, cytomegalovirus, and group A streptococcus, as well as non-infectious conditions like graft-versus-host disease.[4]

Cytokine storms versus cytokine release syndrome

The term "cytokine storm" is often loosely used interchangeably with cytokine release syndrome (CRS) but is more precisely a differentiable syndrome that may represent a severe episode of cytokine release syndrome or a component of another disease entity, such as macrophage activation syndrome. When occurring as a result of a therapy, CRS symptoms may be delayed until days or weeks after treatment. Immediate-onset (fulminant) CRS appears to be a cytokine storm.[5]

Cause

Nutritional deficiency

Magnesium decreases inflammatory cytokine production by modulation of the immune system.[6][7]

Nicotinamide (Vitamin B3) is a potent inhibitor of proinflammatory cytokines.[8][9]

History

The first reference to the term cytokine storm in the published medical literature appears to be by Ferrara et al. in 1993 in a discussion of graft vs. host disease; a condition in which the role of excessive and self-perpetuating cytokine release had already been under discussion for many years.[10][11] The term next appeared in a discussion of pancreatitis in 2002, and in 2003 it was first used in reference to a reaction to an infection.[10]

It is believed that cytokine storms were responsible for the disproportionate number of healthy young adult deaths during the 1918 influenza pandemic, which killed 50 to 100 million people. In this case, a healthy immune system may have been a liability rather than an asset.[12] Preliminary research results from Taiwan also indicated this as the probable reason for many deaths during the SARS epidemic in 2003.[13] Human deaths from the bird flu H5N1 usually involve cytokine storms as well.[14] Cytokine storm has also been implicated in hantavirus pulmonary syndrome.[15]

In 2006, a study at Northwick Park Hospital in England resulted in all 6 of the volunteers given the drug theralizumab becoming critically ill, with multiple organ failure, high fever, and a systemic inflammatory response.[16] Parexel, a company conducting trials for pharmaceutical companies, in one of its documents, wrote about the trial and said theralizumab could cause a cytokine storm—the dangerous reaction the men experienced.[17]

During the COVID-19 pandemic, many deaths were attributable to cytokine storms.[18][19]

References

  1. ↑ Farsalinos, Konstantinos; Barbouni, Anastasia; Niaura, Raymond (2020). "Systematic review of the prevalence of current smoking among hospitalized COVID-19 patients in China: Could nicotine be a therapeutic option?". Internal and Emergency Medicine. doi:10.1007/s11739-020-02355-7. PMID 32385628. 
  2. ↑ Wong, Jonathan P.; Viswanathan, Satya; Wang, Ming; Sun, Lun-Quan; Clark, Graeme C.; D'Elia, Riccardo V. (February 2017). "Current and future developments in the treatment of virus-induced hypercytokinemia". Future Medicinal Chemistry 9 (2): 169–178. doi:10.4155/fmc-2016-0181. ISSN 1756-8927. PMID 28128003. 
  3. ↑ Liu, Qiang; Zhou, Yuan-hong; Yang, Zhan-qiu (January 2016). "The cytokine storm of severe influenza and development of immunomodulatory therapy". Cellular & Molecular Immunology 13 (1): 3–10. doi:10.1038/cmi.2015.74. ISSN 2042-0226. PMID 26189369. PMC 4711683. https://pubmed.ncbi.nlm.nih.gov/26189369/?from_term=cytokine+storm&from_pos=4. 
  4. ↑ Tisoncik, Jennifer R.; Korth, Marcus J.; Simmons, Cameron P.; Farrar, Jeremy; Martin, Thomas R.; Katze, Michael G. (2012). "Into the Eye of the Cytokine Storm". Microbiology and Molecular Biology Reviews 76 (1): 16–32. doi:10.1128/MMBR.05015-11. ISSN 1092-2172. PMID 22390970. 
  5. ↑ "Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel". Journal of Hematology & Oncology 11 (1): 35. March 2018. doi:10.1186/s13045-018-0571-y. PMID 29499750. 
  6. ↑ Sugimoto J, Romani AM, Valentin-Torres AM, Luciano AA, Ramirez Kitchen CM, Funderburg N (2012). "Magnesium decreases inflammatory cytokine production: a novel innate immunomodulatory mechanism.". J Immunol 188 (12): 6338–46. doi:10.4049/jimmunol.1101765. PMID 22611240. 
  7. ↑ Nielsen FH (2018). "Magnesium deficiency and increased inflammation: current perspectives.". J Inflamm Res 11: 25–34. doi:10.2147/JIR.S136742. PMID 29403302. 
  8. ↑ Ungerstedt JS, Blömback M, Söderström T (2003). "Nicotinamide is a potent inhibitor of proinflammatory cytokines.". Clin Exp Immunol 131 (1): 48-52. doi:10.1046/j.1365-2249.2003.02031.x. PMID 12519385. PMC 1808598. https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12519385. 
  9. ↑ Yanez M, Jhanji M, Murphy K, Gower RM, Sajish M, Jabbarzadeh E (2019). "Nicotinamide Augments the Anti-Inflammatory Properties of Resveratrol through PARP1 Activation.". Sci Rep 9 (1): 10219. doi:10.1038/s41598-019-46678-8. PMID 31308445. PMC 6629694. https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31308445. 
  10. ↑ 10.0 10.1 "The advent of the cytokine storm". Immunology and Cell Biology 85 (4): 271–3. June 2007. doi:10.1038/sj.icb.7100062. PMID 17551531. http://www.nature.com:80/icb/journal/v85/n4/full/7100062a.html. 
  11. ↑ "Cytokine storm of graft-versus-host disease: a critical effector role for interleukin-1". Transplantation Proceedings 25 (1 Pt 2): 1216–7. February 1993. PMID 8442093. 
  12. ↑ "Preparing for the next pandemic". The New England Journal of Medicine 352 (18): 1839–42. May 2005. doi:10.1056/NEJMp058068. PMID 15872196. 
  13. ↑ "An interferon-gamma-related cytokine storm in SARS patients". Journal of Medical Virology 75 (2): 185–94. February 2005. doi:10.1002/jmv.20255. PMID 15602737. 
  14. ↑ "Confronting potential influenza A (H5N1) pandemic with better vaccines". Emerging Infectious Diseases 13 (10): 1512–8. October 2007. doi:10.3201/eid1310.061262. PMID 18258000. 
  15. ↑ "High levels of cytokine-producing cells in the lung tissues of patients with fatal hantavirus pulmonary syndrome". The Journal of Infectious Diseases 179 (2): 295–302. February 1999. doi:10.1086/314597. PMID 9878011. 
  16. ↑ The Lancet Oncology (February 2007). "High stakes, high risks". The Lancet. Oncology 8 (2): 85. doi:10.1016/S1470-2045(07)70004-9. PMID 17267317. 
  17. ↑ Coghlan A (2006-08-14). "Mystery over drug trial debacle deepens". Health. New Scientist. https://www.newscientist.com/article/dn9734-mystery-over-drug-trial-debacle-deepens-.html. 
  18. ↑ "COVID-19: consider cytokine storm syndromes and immunosuppression". Lancet 395 (10229): 1033–1034. March 2020. doi:10.1016/S0140-6736(20)30628-0. PMID 32192578. PMC 7270045. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30628-0/fulltext. 
  19. ↑ "Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China". Intensive Care Medicine 46 (5): 846–848. March 2020. doi:10.1007/s00134-020-05991-x. PMID 32125452. 



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