Pathophysiology
Clinical meaning
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.