IL-1, IL-18, and IL-33 families of cytokines

Authors

  • William P. Arend,

    1. Division of Rheumatology, University of Colorado Denver, School of Medicine, Denver, CO, USA.
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  • Gaby Palmer,

    1. Division of Rheumatology, University Hospital of Geneva, Geneva, Switzerland.
    2. Department of Pathology and Immunology, University of Geneva School of Medicine, Geneva, Switzerland.
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  • Cem Gabay

    1. Division of Rheumatology, University Hospital of Geneva, Geneva, Switzerland.
    2. Department of Pathology and Immunology, University of Geneva School of Medicine, Geneva, Switzerland.
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William P. Arend, MD
Division of Rheumatology B115
School of Medicine
University of Colorado Denver
1775 North Ursula St.
PO Box 6511
Aurora, CO 80045
USA
Tel.: +1 303 724 7582
Fax: +1 303 724 7581
e-mail: william.arend@uchsc.edu

Abstract

Summary: The interleukin-1 (IL-1), IL-18, and IL-33 families of cytokines are related by mechanism of origin, receptor structure, and signal transduction pathways utilized. All three cytokines are synthesized as precursor molecules and cleaved by the enzyme caspase-1 before or during release from the cell. The NALP-3 inflammasome is of crucial importance in generating active caspase-1. The IL-1 family contains two agonists, IL-1α and IL-1β, a specific inhibitor, IL-1 receptor antagonist (IL-1Ra), and two receptors, the biologically active type IL-1R and inactive type II IL-1R. Both IL-1RI and IL-33R utilize the same interacting accessory protein (IL-1RAcP). The balance between IL-1 and IL-1Ra is important in preventing disease in various organs, and excess production of IL-1 has been implicated in many human diseases. The IL-18 family also contains a specific inhibitor, the IL-18-binding protein (IL-18BP), which binds IL-18 in the fluid phase. The IL-18 receptor is similar to the IL-1 receptor complex, including a single ligand-binding chain and a different interacting accessory protein. IL-18 provides an important link between the innate and adaptive immune responses. Newly described IL-33 binds to the orphan IL-1 family receptor T1/ST2 and stimulates T-helper 2 responses as well as mast cells.

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