Biological and clinical roles of IL-18 in inflammatory diseases

  • Nat Rev Rheumatol. 2024 Jan;20(1):33-47. doi: 10.1038/s41584-023-01053-w.
Emily Landy  1 ,  Hallie Carol  2  3 ,  Aaron Ring  4 ,  Scott Canna  5  6  7
Affiliations
  • 1. Program in Microbiology and Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
  • 2. Division of Rheumatology and Immune Dysregulation Program, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • 3. Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • 4. Translational Science and Therapeutics, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • 5. Program in Microbiology and Immunology, University of Pittsburgh, Pittsburgh, PA, USA. [email protected].
  • 6. Division of Rheumatology and Immune Dysregulation Program, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. [email protected].
  • 7. Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. [email protected].
PMID: 38081945 DOI: 10.1038/s41584-023-01053-w
Abstract

Several new discoveries have revived interest in the pathogenic potential and possible clinical roles of IL-18. IL-18 is an IL-1 family cytokine with potent ability to induce IFNγ production. However, basic investigations and now clinical observations suggest a more complex picture. Unique aspects of IL-18 biology at the levels of transcription, activation, secretion, neutralization, receptor distribution and signalling help to explain its pleiotropic roles in mucosal and systemic inflammation. Blood biomarker studies reveal a cytokine for which profound elevation, associated with detectable 'free IL-18', defines a group of autoinflammatory diseases in which IL-18 dysregulation can be a primary driving feature, the so-called 'IL-18opathies'. This impressive specificity might accelerate diagnoses and identify patients amenable to therapeutic IL-18 blockade. Pathogenically, human and animal studies identify a preferential activation of CD8+ T cells over Other IL-18-responsive lymphocytes. IL-18 agonist treatments that leverage the site of production or subversion of endogenous IL-18 inhibition show promise in augmenting immune responses to Cancer. Thus, the unique aspects of IL-18 biology are finally beginning to have clinical impact in precision diagnostics, disease monitoring and targeted treatment of inflammatory and malignant diseases.