Cytokine Cascade

Cytokines are small signaling proteins that orchestrate the immune and inflammatory response. In the innate immune response, pattern recognition receptors (TLRs) on macrophages and dendritic cells detect pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), triggering NF-κB activation and release of pro-inflammatory cytokines: TNF-alpha (first cytokine released; activates endothelium, induces acute phase response), IL-1 (fever, neutrophil activation), IL-6 (acute phase protein synthesis by liver, B-cell differentiation). The cytokine cascade can become dysregulated, leading to cytokine storm -- a massive, self-amplifying release of pro-inflammatory cytokines causing SIRS, septic shock, multi-organ failure, and death. Anti-inflammatory cytokines (IL-10, TGF-beta) normally counterregulate, but in cytokine storm this homeostasis is overwhelmed.