IL18

Overview

IL18 encodes interleukin-18, a pro-inflammatory cytokine of the interleukin-1 family. It is produced as an inactive precursor and becomes biologically active after proteolytic processing, classically by caspase-1 during inflammasome activation. Mature IL-18 promotes inflammatory signaling and can amplify innate and adaptive immune responses, including interferon-γ production and activation of natural killer cells and T lymphocytes. Because of these functions, IL18 is widely studied in inflammatory disease, metabolic dysfunction, tissue injury, and cancer immunology.

In biomedical research, IL-18 is often used as a readout of inflammasome activity alongside interleukin-1 beta, TNF, and Gasdermin D-related pyroptosis markers. It is also explored as a therapeutic payload or immune-modulating factor in cell-based cancer strategies, including IL-18-armed CAR-T cells and engineered extracellular vesicles. Its relevance spans rheumatoid arthritis, obesity-associated metabolic disease, renal injury, neuroinflammation, skin inflammation, and antitumor immunity.

Focus of Latest Publications

Recent studies have used IL18 primarily as a marker and mediator of inflammatory signaling, especially in pathways involving NLRP3, CASP1, and Gasdermin D. In a rheumatoid arthritis model, the “Tianyu” formulation was reported to alleviate disease by modulating the NLRP3/Caspase-1/GSDMD-mediated pyroptosis pathway, with IL-1β, IL-18, and TNF-α measured in cell culture supernatants as inflammatory outputs. Similarly, emodin was shown to attenuate Fusobacterium necrophorum-induced pyroptosis in dairy cow interdigital skin fibroblasts by downregulating NLRP3 and reducing GSDMD, ASC, Caspase-1, IL-1β, and IL-18. A related neuroinflammation study found that inhibition of the microglial cGAS-STING pathway reduced pyroptosis-dependent cytokine release, including IL-1β and IL-18, in mice with intraventricular hemorrhage.

IL18 was also examined in metabolic and organ-injury contexts. A prospective cohort study evaluated the effect of nutritional intervention on interleukin-18 and alpha-2-macroglobulin in women with obesity and metabolic dysfunction-associated fatty liver disease, indicating interest in IL-18 as a biomarker of metabolic inflammation. In renal toxicity research, tramadol exposure was associated with increased renal damage biomarkers including IL-18, and chrysin attenuated this injury alongside broader regulation of RNA networks, antioxidant pathways, and ketogenic metabolism. In cutaneous toxicity induced by osimertinib, IL18 was among the inflammatory factors upregulated by the drug, while glycyrrhizic acid reduced inflammatory signaling in that setting. In skin fibroblasts under pro-inflammatory conditions, lemon balm-derived nanovesicles reduced IL-18, consistent with a role for IL-18 in inflammatory skin disease activity.

IL18 also appears in studies of systemic inflammatory disease and biomarker profiling. A systematic review and meta-analysis of periodontitis reported significantly higher circulating IL-18 among affected individuals, alongside IL-1β, IL-6, IL-17, leptin, MMP-8, MPO, RANKL, and TNF-α. In arthritis-related work, IL-18 was repeatedly measured together with IL-1β and TNF as part of inflammatory readouts in collagen-induced arthritis and related models, including assessments of paw volume, arthritis scores, anti-CCP, and histologic changes.

Beyond its role as a biomarker, IL18 is being actively engineered as an immunotherapy component. One study reported single-day production of non-activated CAR T cells engineered to secrete IL-18, describing IL-18 as a pro-inflammatory cytokine that enhances T-cell function and supports a durable, stemlike state with improved persistence. Another study engineered extracellular vesicles from IL-18-overexpressing tumor cells, with or without TGF-β1 or IL-10 suppression, to create a more immunogenic antigen source for next-generation dendritic cell vaccines. In parallel, IL-12/15/18 cytokine priming was used to generate cytokine-induced memory-like natural killer cells with enhanced antitumor activity, proliferation, and persistence, underscoring the broader immunostimulatory context in which IL-18 is used.