Interleukin- 18: Potential Biomarker for Various Diseases

Interleukin 18 (IL-18) is a cytokine that has been found to be involved in many different biological processes. So what is a cytokine? A cytokine is protein that is secreted by certain cells and interacts/communicates between cells. And which cells produce IL-18?  IL-18 is produced by dendritic cells, monocytes, macrophages, neutrophils and epithelial cells. IL-18 is unique in that it has two forms, mature IL-18 and pro IL-18. IL-18 is first present as proform 24kd precursor and lacks the signal sequence required for secretion1. However, it is the active form of IL-18 that is present in many different tissue types2. IL-18 is cleaved so it can be in its active form. ICE (IL-1β Converting Enzyme) or Caspase 1 cleaves Pro-IL-18 after Asp35, leading to the active form of IL-18, measuring at 18 kDa2. This activation has shown to be an important aspect of immune defense. 

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. IL-18 has a role in various diseases. High levels of IL-18 are detected in the blood of patient with allergic diseases (bronchial asthma, atopic dermatitis, allergic rhinitis, etc.) and those with autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus (SLE), Adult Still’s disease, multiple sclerosis, Crohn’s disease, ulcerative colitis, etc.). IL-18 is also 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.Results can lead to therapeutic remedies since it appears that IL-18 has significant involvement in early immune response.

Automimmune diseases with higher levels of IL-18:

  • Rheumatoid arthritis (RA)
  • Adult Still's Disease
  • Inflammatory bowel diseases (UC,CD)
  • Systemic lupus erythematosus (SLE)
  • Multiple Sclerosis
  • Systemic juvenile idiopathic arthritis
  • Macrophage activation syndrome