Cytokine storms

A cytokine storm, also known as hypercytokinemia, is a severe immune reaction where the body releases excessive levels of cytokines, leading to systemic inflammation and potentially life-threatening organ damage. This phenomenon can be triggered by infections (e.g., influenza, COVID-19), autoimmune disorders, and certain therapies like CAR T-cell therapy. Key cytokines involved include interleukin-1, interleukin-6, and TNF, which can cause symptoms such as fever, fatigue, and acute respiratory distress syndrome (ARDS). Effective management often involves immunosuppressive therapies targeting specific cytokines.
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what are the main triggers that can lead to a cytokine storm
Cytokine storms can be triggered by a variety of factors, including:
  1. Infections: Viral infections such as H1N1 influenza, H5N1 influenza, SARS-CoV-1, SARS-CoV-2, Epstein-Barr virus, and cytomegalovirus are common triggers. Bacterial infections like group A streptococcus can also cause cytokine storms.
  2. Autoimmune Disorders: Conditions such as systemic juvenile idiopathic arthritis and macrophage activation syndrome can lead to cytokine storms.
  3. Immunotherapy: Treatments like CAR T-cell therapy can induce cytokine release syndrome, which can escalate into a cytokine storm.
  4. Non-infectious Conditions: Graft-versus-host disease and post-cardiac arrest syndrome are examples of non-infectious triggers.
what role do cytokines play in the immune response during a cytokine storm
Cytokines are crucial in coordinating the immune response during a cytokine storm. They act as signaling molecules that regulate the activity of immune cells, promoting inflammation and recruiting additional immune cells to the site of infection or injury. Key cytokines involved include interleukin-1, interleukin-6, TNF, and interferon-γ, which can lead to systemic inflammation and organ damage when produced in excess. This overproduction creates a positive feedback loop, amplifying the immune response and potentially causing severe tissue damage and multi-organ failure.
how do cytokines like interferon-γ and interleukin-1 contribute to the severity of a cytokine storm
Cytokines like interferon-γ (IFN-γ) and interleukin-1 (IL-1) play significant roles in the severity of a cytokine storm by promoting inflammation and immune cell activation.
  • Interferon-γ (IFN-γ): Primarily secreted by activated T cells and NK cells, IFN-γ is a potent activator of macrophages. It induces fever, chills, headache, dizziness, and fatigue. Elevated levels of IFN-γ can lead to prolonged activation of immune cells, contributing to systemic inflammation and tissue damage.
  • Interleukin-1 (IL-1): IL-1 is encoded by two genes (IL1A and IL1B) and binds to the interleukin-1 receptor, activating intracellular signaling pathways like NF-κB. IL-1 can induce fever and promote the secretion of other proinflammatory cytokines, exacerbating the inflammatory response and contributing to organ damage.
Both cytokines are central to the pathophysiology of cytokine storms, driving hyperinflammation and multi-organ dysfunction.
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