Elsevier

Methods

Volume 19, Issue 1, September 1999, Pages 121-132
Methods

Regular Article
Interleukin-18

https://doi.org/10.1006/meth.1999.0837Get rights and content

Abstract

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) γ 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 IFNγ production in T cells and natural killer (NK) cells. Mice deficient in IL-18 have suppressed IFNγ 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-1β share primary amino acid sequences of the so-called “signature sequence” motif and are similarly folded as all-β pleated sheet molecules. Also similar to IL-1β, 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-1β-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-18Rα, 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 κB (NFκB)-inducing kinase (NIK) with subsequent activation of NFκB. 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.

References (82)

  • P. Parnet et al.

    J. Biol. Chem.

    (1996)
  • L. Shapiro et al.

    Exp. Cell Res.

    (1997)
  • K. Takeda et al.

    Immunity

    (1998)
  • G. Fantuzzi et al.

    Blood

    (1998)
  • D. Robinson et al.

    Immunity

    (1997)
  • K. Torigoe et al.

    J. Biol. Chem.

    (1997)
  • T.L. Born et al.

    J. Biol. Chem.

    (1998)
  • S.A. Greenfeder et al.

    J. Biol. Chem.

    (1995)
  • H. Engelmann et al.

    J. Biol. Chem.

    (1990)
  • D. Novick et al.

    J. Chromatogr.

    (1990)
  • D. Novick et al.

    Cell

    (1994)
  • G.E. Croston et al.

    J. Biol. Chem.

    (1995)
  • H. Wesche et al.

    J. Biol. Chem.

    (1997)
  • H. Kojima et al.

    Biochem. Biophys. Res. Commun.

    (1998)
  • O. Adachi et al.

    Immunity

    (1998)
  • K. Tsuji-Takayama et al.

    Biochem. Biophys. Res. Commun.

    (1997)
  • S. Matsumoto et al.

    Biochem. Biophys. Res. Commun.

    (1997)
  • K. Kobayashi et al.

    Clin. Immunol. Immunopathol.

    (1998)
  • M. Taniguchi et al.

    J. Immunol. Methods

    (1997)
  • C.A. Dinarello

    Blood

    (1996)
  • A.J. Puren et al.

    Eur. Cytokine Netw.

    (1998)
  • M.D. Mileno et al.

    J. Infect. Dis.

    (1995)
  • M. Tone et al.

    J. Immunol.

    (1997)
  • T.J. Martin et al.

    Crit. Rev. Eukaryot. Gene Expr.

    (1998)
  • S. Stoll et al.

    J. Immunol.

    (1997)
  • T. Sareneva et al.

    J. Immunol.

    (1998)
  • G. Trinchieri

    Annu. Rev. Immunol.

    (1995)
  • C.A. Hunter et al.

    J. Immunol.

    (1995)
  • K. Barbulescu et al.

    J. Immunol.

    (1998)
  • Y. Gu et al.

    Science

    (1997)
  • T. Ghayur et al.

    Nature

    (1997)
  • D. Novick et al.

    Eur. Cytokine Netw.

    (1998)
  • M. Munder et al.

    J. Exp. Med.

    (1998)
  • T. Ohtsuki et al.

    Anticancer Res.

    (1997)
  • L. Shapiro et al.

    Proc. Natl. Acad. Sci. USA

    (1998)
  • H. Okamura et al.

    Nature

    (1995)
  • Y. Gu et al.

    EMBO J.

    (1995)
  • A.J. Puren et al.

    J. Clin. Invest.

    (1998)
  • S. Szabo et al.

    J. Exp. Med.

    (1997)
  • D. Xu et al.

    J. Exp. Med.

    (1998)
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