A cytokine storm is a severe inflammatory reaction in which the immune system releases large amounts of pro‑inflammatory cytokines, leading to systemic tissue damage and organ dysfunction.
Explanation
Cytokine storm refers to a positive feedback loop of immune activation triggered by infections or immune therapies. When pattern‑recognition receptors on innate immune cells detect viral, bacterial or fungal components, they induce production of cytokines such as tumor necrosis factor, interleukin‑1, interleukin‑6, interferon‑γ and chemokines. In normal responses these mediators recruit leukocytes and promote pathogen clearance. In a storm, the signals amplify uncontrollably and lead to widespread endothelial activation, vascular leakage, clotting abnormalities and multi‑organ failure. Genetic predisposition, viral virulence factors and underlying health conditions influence susceptibility. Viral infections like influenza A/H5N1, SARS‑CoV‑2 and hantavirus pulmonary syndrome, and bacterial sepsis can trigger this syndrome. Therapies that stimulate T cells, including chimeric antigen receptor T‑cell therapy and immune checkpoint inhibitors, can also cause cytokine release syndrome, a similar condition. Management involves supportive care, suppression of the hyper‑inflammatory state with corticosteroids, inhibitors of interleukin‑6 receptors or JAK inhibitors, and treatment of the underlying infection.
Illustrative cases
During the 1918 influenza pandemic many young adults died from over‑exuberant immune responses rather than direct viral cytolysis. Severe cases of COVID‑19 are marked by high serum levels of IL‑6, C‑reactive protein and ferritin, and patients often benefit from corticosteroids or IL‑6 receptor blockers. H5N1 avian influenza infection in humans can trigger fulminant cytokine release, leading to pulmonary edema and acute respiratory distress syndrome. Cytokine release syndrome is a predictable adverse event in CAR T‑cell therapy for leukemia and lymphoma; clinicians monitor patients closely and administer IL‑6 receptor blockers when necessary. Macrophage activation syndrome in systemic juvenile idiopathic arthritis and hemophagocytic lymphohistiocytosis are non‑infectious examples of cytokine storm.
Cytokine storms exemplify how an overactive immune response can be as harmful as the pathogen. Recognition of this phenomenon has led to targeted anti‑inflammatory treatments that improve outcomes in severe viral infections and immunotherapies.
Related Terms: Hyperinflammation, IL‑6, Sepsis, Cytokine release syndrome, Hemophagocytic lymphohistiocytosis