Clinical Information

Cytokines play a pivotal role in both innate and adaptive immune pathways by mediating diverse cellular functions. Elevated cytokines have been reported in infection, autoimmune diseases, malignancy, post-transplant states, immune deficiency with dysregulation, and after immunomodulatory therapy. Cytokine levels have demonstrated utility as biomarkers in autoinflammatory and autoimmune diseases and for monitoring treatment responses to biologics. Multiplex cytokine profiling can reveal characteristic patterns, including broad elevation of pro-inflammatory mediators (such as interleukin [IL]-6, tumor necrosis factor alpha [TNF-alpha], IL-8) in systemic inflammation, increased Th1-type cytokines (such as IFN-gamma, IL-2) in cell-mediated activation, and elevated Th2-type cytokines (such as IL-4, IL-5, IL-13) in allergic or certain antibody-mediated processes, while increased IL-10 or soluble IL-2 receptor may indicate regulatory activation or lymphoproliferation. Cytokine serum panels can help distinguish IL-1beta-driven autoinflammatory syndromes (eg, familial Mediterranean fever) from conditions more strongly associated with TNF-alpha and IL-6 (eg, rheumatoid arthritis). Elevated levels of soluble IL-2R and IL-10, often accompanied by increased interferon gamma (IFN-gamma) and IL-6, have been shown to differentiate complicated common variable immunodeficiency (CVID) patients with autoimmunity and/or lymphoproliferation from those with predominantly infection-only phenotypes. The cytokine storm (CS), observed in sepsis, CAR-T cell therapy, COVID-19 infection and other infectious and noninfectious conditions, is characterized by markedly increased circulating cytokine levels due to overactivation of immune cells. Measuring cytokine levels following CAR-T cell therapy is important for characterizing therapy-induced toxicities such as cytokine release syndrome (CRS). Elevations in cytokines including IL-1beta, IL-2, IL-6, IL-8, IL-10, IFN-gamma, and TNF-alpha have been reported in CRS, with higher and earlier peaks within the first week after infusion generally correlating with greater severity. Characterization of CS and CRS facilitates earlier and more targeted intervention with available cytokine-directed treatments (such as antibodies targeting IL-1, IL-6, TNF-alpha, IFN-gamma) in appropriate clinical contexts, to improve outcomes and reduce the risk of life-threatening complications.