Methods. 1999 Sep;19(1):121-32. doi: 10.1006/meth.1999.0837.


Interleukin (IL)-18 is a newly discovered cytokine, structurally similar to IL-1, with profound effects on T-cell activation. This short review summarizes the present knowledge on IL-18, to give an insight into the future perspectives for its possible use as vaccine adjuvant. Formerly called interferon (IFN) gamma inducing factor (IGIF), IL-18 is the new name of a novel cytokine that plays an important role in the T-cell-helper type 1 (Th1) response, primarily by its ability to induce IFNgamma production in T cells and natural killer (NK) cells. Mice deficient in IL-18 have suppressed IFNgamma production despite the presence of IL-12 IL-18 is related to the IL-1 family in terms of structure, receptor family, and function. In terms of structure, IL-18 and IL-1beta share primary amino acid sequences of the so-called "signature sequence" motif and are similarly folded as all-beta pleated sheet molecules. Also similar to IL-1beta, IL-18 is synthesized as a biologically inactive precursor molecule lacking a signal peptide which requires cleavage into an active, mature molecule by the intracellular cysteine protease called IL-1beta-converting enzyme (ICE, also called caspase-1). The activity of mature IL-18 is closely related to that of IL-1. IL-18 induces gene expression and synthesis of tumor necrosis factor (TNF), IL-1, Fas ligand, and several chemokines. The activity of IL-18 is via an IL-18 receptor (IL-18R) complex. This IL-18R complex is made up of a binding chain termed IL-18Ralpha, a member of the IL-1 receptor family previously identified as the IL-1 receptor-related protein (IL-1Rrp), and a signaling chain, also a member of the IL-1R family. The IL-18R complex recruits the IL-1R-activating kinase (IRAK) and TNFR-associated factor-6 (TRAF-6) which phosphorylates nuclear factor kappaB (NFkappaB)-inducing kinase (NIK) with subsequent activation of NFkappaB. Thus on the basis of primary structure, three-dimensional structure, receptor family, signal transduction pathways and biological effects, IL-18 appears to be a new member of the IL-1 family. Similar to IL-1, IL-18 participates in both innate and acquired immunity.

Publication types

  • Review

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Cytokines / physiology
  • Humans
  • Infections / immunology
  • Inflammation Mediators / physiology
  • Interferon Inducers / administration & dosage
  • Interferon Inducers / pharmacology
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / administration & dosage
  • Interleukin-18 / administration & dosage
  • Interleukin-18 / pharmacology*
  • Interleukin-18 / physiology*
  • Interleukin-18 Receptor alpha Subunit
  • Keratinocytes / immunology
  • Macrophages / immunology
  • Mice
  • Monocytes / immunology
  • Neoplasms / immunology
  • Receptors, Interleukin / physiology
  • Receptors, Interleukin-18
  • Signal Transduction
  • Th1 Cells / immunology


  • Adjuvants, Immunologic
  • Cytokines
  • IL18R1 protein, human
  • Il18r1 protein, mouse
  • Inflammation Mediators
  • Interferon Inducers
  • Interleukin-18
  • Interleukin-18 Receptor alpha Subunit
  • Receptors, Interleukin
  • Receptors, Interleukin-18
  • Interleukin-12
  • Interferon-gamma