Detection of Free Bioactive IL-18 and IL-18BP in Inflammatory Disorders

The interleukin (IL)-18 cytokine plays an important driver role in a range of autoimmune and inflammatory diseases, as well as cancer. IL-18 is a potent inducer of interferon gamma (IFN-γ), and the bioactivity of IL-18 is regulated by its natural soluble inhibitor, IL-18-binding protein (IL-18BP), which is present at high concentrations in the circulation. Many cell types have been described to secrete IL-18BP, constitutively or under the influence of IFN-γ, thus generating a negative feedback loop for IL-18. Therefore, solely measuring total IL-18 protein levels does not allow to evaluate its biological activity, especially in the context of systemic inflammatory diseases or other circumstances where IL-18BP is present (e.g., samples containing plasma, cells constitutively expressing IL-18BP). Considering there is a critical need to accurately measure the protein levels of both mature, biologically active IL-18 and IL-18BP as biomarkers of disease activity in patients and also stratification for potential anti-IL-18 therapy, in this chapter we provide the latest techniques to measure mature, free, and bioactive IL-18 and IL-18BP in different samples.