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.

Key Publications

• NEWJun Decoding neuron-specific lineage to identify diagnostic biomarkers and therapeutic targets for ischemic stroke. (iScience, 2026, PMID 42291234): "This model was rigorously validated across multi-omics datasets and species."
• May The "Tianyu" Formulation Alleviates Rheumatoid Arthritis by Modulating the NLRP3/Caspase-1/GSDMD-Mediated Pyroptosis Pathway. (FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2026, PMID 42033182): "...by measuring the release of lactate dehydrogenase (LDH) and inflammatory factors (interleukin [IL]-1β, IL-18, TNF-α) in the cell culture supernatants."
• May Effect of nutritional intervention on interleukin-18 and alpha-2-macroglobulin in women with obesity and metabolic dysfunction-associated fatty liver disease: a prospective cohort study. (Journal of health, population, and nutrition, 2026, PMID 42116229): "Effect of nutritional intervention on interleukin-18 and alpha-2-macroglobulin in women with obesity and metabolic dysfunction-associated fatty liver disease: a prospective cohort study."
• May Fuzheng Jiedu Tongluo Granule Alleviates Cerebral Ischemia/reperfusion Injury-induced Inflammation By Inhibiting Drp1-mediated TXNIP/NLRP3 Pathway. (Molecular neurobiology, 2026, PMID 42113382): "FZJDTL inhibited the production of ROS and inflammatory factors (IL-1β, IL-18)."
• May Chrysin attenuates tramadol-driven renal dysfunction via regulation of RNA networks, antioxidant pathways, and ketogenic metabolism. (European journal of pharmacology, 2026, PMID 42002091): "The administration of TR resulted in substantial elevations in serum creatinine and BUN levels, concurrently increasing renal damage biomarkers including KIM-1, NGAL, FABP, IL-18, MCP-1, and YKL-40."
• Apr Inhibition of the Microglial cGAS-STING Pathway Improves Neurological Deficits and Long-Term Hydrocephalus Symptoms in Mice with Intraventricular Hemorrhage. (Molecular neurobiology, 2026, PMID 42050115): "Pharmacological inhibition or conditional knockout of cGAS attenuated global neuroinflammation, suppressed microglial activation, and reduced both pyroptosis-dependent (IL-1β and IL-18) and nonpyroptosis-dependent (TNF-α, IFN-β, and IL-6) cytokine release."
• Apr Testosterone-Modified Liposomes Loaded with the Zn-Polyphenol Complex for Treatment of Male Infertility. (ACS applied materials & interfaces, 2026, PMID 41985533): "...and reduced inflammatory cytokines, such as IL-1β and IL-18..."
• Apr Single-day nonactivated IL-18-armed CAR T cells establish a durable, stemlike state with enhanced persistence. (Blood, 2026, PMID 41990270): "Here, we report the single day production of non-activated CAR T-cells engineered to secrete interleukin-18 (IL-18), a pro-inflammatory cytokine that enhances T-cell function."
• Apr Exercise-mobilized lymphocytes enhance the function of cytokine-induced memory-like NK cells against myeloid leukemia. (Blood advances, 2026, PMID 41538301): "Short-term activation of natural killer (NK) cells with interleukin-12 (IL-12), IL-15, and IL-18 (IL-12/15/18) gives rise to cytokine-induced memory-like (CIML) NK cells after adoptive transfer, which exhibit enhanced antitumor activity, proliferation, and persistence."
• Apr Glycyrrhizic Acid Alleviates Osimertinib-Induced Cutaneous Toxicity by Inhibiting Keratinocyte Apoptosis and Inflammation. (Phytotherapy research : PTR, 2026, PMID 41920265): "Osimertinib upregulated inflammatory factors including CCL2, CCL27, and IL18."