Cytokine storm

Source: Wikipedia, the free encyclopedia.
Cytokine storm
Other nameshypercytokinemia
SpecialtyImmunology

A cytokine storm, also called hypercytokinemia, is a pathological 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. Cytokines are a normal part of the body's immune response to infection, but their sudden release in large quantities may cause multisystem organ failure and death.[1]

Cytokine storms may be caused by infectious or non-infectious

chemokines, activating macrophages, dendritic cells, and others.[5]

Cytokine storm syndrome is a diverse set of conditions that can result in a cytokine storm. Cytokine storm syndromes include familial

idiopathic arthritis–associated macrophage activation syndrome, NLRC4 macrophage activation syndrome, cytokine release syndrome and sepsis.[6]

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.[7]

Research

Nicotinamide (a form of vitamin B3) is a potent inhibitor of proinflammatory cytokines.[8][9] Low blood plasma levels of trigonelline (one of the metabolites of vitamin B3) have been suggested for the prognosis of SARS-CoV-2 death (which is thought to be due to the inflammatory phase and cytokine storm).[10][11]

Magnesium decreases inflammatory cytokine production by modulation of the immune system.[12][13]

History

The first reference to the term cytokine storm in the published

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.[14][15][16] 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.[14]

It is believed that cytokine storms were responsible for the disproportionate number of healthy young adult deaths during the

In 2006, a study at

inflammatory response.[21] Parexel, a company conducting trials for pharmaceutical companies claimed that theralizumab could cause a cytokine storm—the dangerous reaction the men experienced.[22]

Relationship to COVID-19

Cytokine release via activation of JAK/STAT signalling pathway following SARS-Cov-2 infection resulting in ARDS related to COVID-19. Abbreviations: ACE2: Angiotensin-converting enzyme 2, CXCL9: Chemokine (C–X–C motif) ligand 9, IL: interleukin, JAK: Janus kinase, and STAT: signal transducer and activator of transcription.[23]

During the

cardiovascular organs.[23] The higher mortality has been linked to the effects of ARDS aggravation and the tissue damage that can result in organ-failure and/or death.[28]

ARDS was shown to be the cause of mortality in 70% of COVID-19 deaths.

postmortem examination of patients with COVID-19 has shown a large accumulation of inflammatory cells in lung tissues including macrophages and T-helper cells.[30]

Early recognition of a cytokine storm in COVID-19 patients is crucial to ensure the best outcome for recovery, allowing treatment with a variety of biological agents that target the cytokines to reduce their levels. Meta-analysis suggests clear patterns distinguishing patients with or without severe disease. Possible predictors of severe and fatal cases may include "

interleukin-6 (IL-6). Ferritin and IL-6 are considered to be possible immunological biomarkers for severe and fatal cases of COVID-19. Ferritin and C-reactive protein may be possible screening tools for early diagnosis of systemic inflammatory response syndrome in cases of COVID-19.[31]

Due to the increased levels of cytokines and interferons in patients with severe COVID-19, both have been investigated as potential targets for SARS-CoV-2 therapy. An

animal study found that mice producing an early strong interferon response to SARS-CoV-2 were likely to live, but in other cases the disease progressed to a highly morbid overactive immune system.[32][33]
The high mortality rate of COVID-19 in older populations has been attributed to the impact of age on interferon responses.

Short-term use of dexamethasone, a synthetic corticosteroid, has been demonstrated to reduce the severity of inflammation and lung damage induced by a cytokine storm by inhibiting the severe cytokine storm or the hyperinflammatory phase in patients with COVID-19.[34]

Clinical trials continue to identify causes of cytokine storms in COVID-19 cases.[35][36] One such cause is the delayed Type I interferon response that leads to accumulation of pathogenic monocytes. High viremia is also associated with exacerbated Type I interferons response and worse prognosis.[37] Diabetes, hypertension, and cardiovascular disease are all risk factors of cytokine storms in COVID-19 patients.[38]

References

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  10. ^ Caterino, Marianna, Michele Costanzo, Roberta Fedele, Armando Cevenini, Monica Gelzo, Alessandro Di Minno, Immacolata Andolfo et al. "The serum metabolome of moderate and severe COVID-19 patients reflects possible liver alterations involving carbon and nitrogen metabolism." International journal of molecular sciences 22, no. 17 (2021): 9548.
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