From the Guidelines
Cytokine storms are primarily caused by an excessive and uncontrolled release of pro-inflammatory cytokines, such as TNF-α, IL-1, and IL-6, in response to infections like COVID-19, autoimmune conditions, or certain therapies. This hyperactive immune response typically begins when pattern recognition receptors on immune cells detect pathogens or tissue damage, triggering the release of initial cytokines and creating a dangerous positive feedback loop where each wave of activated cells produces more inflammatory mediators 1. Several factors can predispose individuals to cytokine storms, including genetic variations in cytokine genes, underlying autoimmune disorders, and certain infections like influenza, SARS-CoV-2, and Epstein-Barr virus.
Key Factors Contributing to Cytokine Storms
- Genetic variations in cytokine genes
- Underlying autoimmune disorders
- Certain infections like influenza, SARS-CoV-2, and Epstein-Barr virus
- Therapeutic interventions such as CAR-T cell therapy and some monoclonal antibodies
The excessive inflammation damages tissues and organs, potentially leading to multi-organ failure, with the lungs, heart, kidneys, and brain being particularly vulnerable 1. Treatment typically involves immunosuppressive medications like corticosteroids, targeted cytokine inhibitors such as tocilizumab (anti-IL-6), and supportive care to maintain organ function while the inflammatory response resolves. The use of tocilizumab, an IL-6 inhibitor, has shown promise in reducing the requirement of mechanical ventilation and the risk of ICU admission in severe COVID-19 cases 1. However, its use is currently recommended only within clinical trials due to insufficient evidence and potential risks of serious infections.
From the FDA Drug Label
Cytokine Release Syndrome (CRS) (1. 6) Adults and pediatric patients 2 years of age and older with chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome.
The causes of cytokine storm include chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome 2.
- Key causes:
- CAR T cell treatment
- Severe or life-threatening cytokine release syndrome
- Hospitalized adult patients with coronavirus disease 2019 (COVID-19) who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) 2.
From the Research
Causes of Cytokine Storm
- Cytokine storm is a phenomenon characterized by strong elevated circulating cytokines that most often occur after an overreactive immune system is activated by an acute systemic infection 3.
- The pathogenesis of cytokine storm is complex and can be caused by various factors, including viral infections, cancer, sepsis, and multi-organ failure 4.
- In the context of COVID-19, cytokine storm is believed to be responsible for critical illness and is associated with a worse prognosis and increased fatality rate 4, 5.
- The disease progresses rapidly, and the mortality is high, with certain evidence showing that the severe deterioration of some patients has been closely related to the cytokine storm in their bodies 5.
Key Factors Contributing to Cytokine Storm
- Hyperinflammatory response of the body characterized by pathological cytokine levels 6.
- Overreactive immune system activated by an acute systemic infection 3.
- Various cells participating in cytokine storm induction and progression, with profiles of cytokines released during cytokine storm varying from disease to disease 3.
- Type I and II interferons, tumour necrosis factor, and members of the Interleukin family playing a potential role in COVID-19 6.
Implications of Cytokine Storm
- Cytokine storm can lead to severe manifestations of COVID-19, including acute respiratory distress syndrome, thromboembolic diseases, encephalitis, acute kidney injury, and vasculitis 4.
- Understanding the pathogenesis of cytokine storm can help unravel risk factors for the condition and therapeutic strategies to modulate the immune response and deliver improved outcomes in COVID-19 patients at high risk for severe disease 4.