Cytokine release syndrome (CRS)

Cytokine release syndrome (CRS), commonly known as a cytokine storm, is a life-threatening systemic inflammatory condition characterized by the rapid and excessive release of pro-inflammatory cytokines into the circulation. This phenomenon results from a dysregulated immune response where a positive feedback loop between immune cells and cytokines leads to uncontrolled hyperinflammation. It is frequently triggered by severe infections such as COVID-19, influenza, and sepsis, as well as by therapeutic interventions like chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies. The resulting systemic inflammation can cause widespread tissue damage, vascular leakage, acute respiratory distress syndrome (ARDS), and multi-organ failure. Therapeutic management focuses on dampening the immune response through the use of broad-spectrum corticosteroids or targeted biologics that inhibit specific mediators like interleukin-6 (IL-6) or interleukin-1 (IL-1), as well as small molecule inhibitors of signaling pathways such as Janus kinases (JAKs).

Other names

Cytokine stormCytokine storm syndromeHypercytokinemiaSystemic inflammatory response syndromeMacrophage activation syndromeCytokine shock

Drugs treat this condition by antagonizing specific cytokine receptors (e.g., IL-6R, IL-1R), neutralizing circulating cytokines (e.g., TNF-alpha, IL-6), inhibiting intracellular signaling pathways (e.g., JAK/STAT), or providing broad genomic and non-genomic immunosuppression via glucocorticoid receptor activation to interrupt the inflammatory feedback loop.