Interleukin 18 (IL-18), also known as INFγ-inducing factor, is a cytokine that plays key roles in many physiological functions including immunology and metabolic processing. It serves as a biomarker or therapeutic target for a wide array of disease indications. This marker is important in innate and acquired immunity. IL18 has roles in infectious diseases, inflammation, and autoimmunity. Patients with high IL-18 levels display various allergic diseases.
IL-18 has been observed to be produced by dendritic cells, monocytes, macrophages, neutrophils, and epithelial cells. IL-18 facilitates Th1-type immunoreactions by acting on T cells. Stimulation of Th1 cells with IL-18 in the presence of anti-CD3 antibody triggers IL-13 production as well as IFN-γ production. IL-18 action on basophils and mast cells results in complex physiological reactions, including allergic responses. IL-18 binding protein (IL-18BP) is a serum inhibitor of IL-18 activity. In cases where IL-18BP is greater than IL-18, IL-18 activity is suppressed. However, when IL-18 levels are high, inflammatory reactions have been observed, making IL-18 a pro-inflammatory cytokine.
IL-18 exists in two forms- pro IL-18 and mature IL-18. It is first present in the pro-form 24 kd precursor and lacks the signal sequence required for secretion1. ICE (IL-1β Converting Enzyme) or Caspase 1 cleaves Pro-IL-18 after Asp35 activating IL-18. 2 This 18 kD active form is seen in body tissues and carries out IL-18 function, playing a crucial role in the immune defenses.
Role of IL18 in diseases
IL-18 has been shown to have a rapid secretion/activation response. Induction is observed as early as 1 hour after stimulation with anti-CD40. Further, IL-18 is indicated in various disease conditions. High levels of IL-18 are detected in the blood of patients with allergic diseases (bronchial asthma, atopic dermatitis, allergic rhinitis, etc.) and also those with autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus (SLE), Adult Still’s disease, multiple sclerosis, Crohn’s disease, ulcerative colitis, etc.). Additionally it is found in the urine of patients with acute renal disorder3 and appears to mediate the progression of type 2 diabetes4. The regulation and release of IL-18 is still under investigation. This could unlock the therapeutic potential of IL-18 as a biomarker or a drug target.
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Data using MBL International Products