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Interleukin-18
1Division of Infectious Diseases, B168, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, Colorado 80262, USA.
Methods (San Diego, Calif.)
|October 20, 1999
Summary
Interleukin-18 (IL-18), a cytokine similar to IL-1, is crucial for T-cell activation and induces interferon-gamma production. Its structural and functional similarities suggest it
Area of Science:
- Immunology
- Cytokine Biology
- Molecular Biology
Background:
- Interleukin-18 (IL-18), formerly interferon-gamma inducing factor (IGIF), is a novel cytokine.
- IL-18 plays a critical role in T-cell-helper type 1 (Th1) responses by inducing interferon-gamma (IFNγ) production in T cells and natural killer (NK) cells.
- Mice lacking IL-18 exhibit suppressed IFNγ production, even with IL-12 present.
Purpose of the Study:
- To review current knowledge on Interleukin-18 (IL-18).
- To explore the potential of IL-18 as a vaccine adjuvant.
Main Methods:
- Structural and functional comparison of IL-18 with the IL-1 family.
- Analysis of IL-18 precursor activation via IL-1beta-converting enzyme (ICE/caspase-1).
- Investigation of IL-18 receptor (IL-18R) complex signaling pathways, including IRAK, TRAF-6, NIK, and NFκB.
Main Results:
- IL-18 shares structural similarities with IL-1beta, including a conserved motif and beta-sheet folding.
- IL-18 is synthesized as an inactive precursor requiring intracellular cleavage for activation.
- IL-18 signaling involves an IL-18R complex that activates NFκB through IRAK, TRAF-6, and NIK.
Conclusions:
- IL-18 is a new member of the IL-1 cytokine family based on its structure, receptor, signaling, and biological effects.
- IL-18 is involved in both innate and acquired immunity.
- IL-18 holds promise as a potential vaccine adjuvant.