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

Immunol Rev. 2008 Jun;223:20-38. doi: 10.1111/j.1600-065X.2008.00624.x.

Abstract

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-1alpha and IL-1beta, 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.

Publication types

  • Review

MeSH terms

  • Alternative Splicing / immunology
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology
  • Humans
  • Immune System Diseases / genetics
  • Immune System Diseases / immunology*
  • Immune System Diseases / pathology
  • Immune System Diseases / therapy
  • Immunotherapy
  • Interleukin-1 / chemistry
  • Interleukin-1 / immunology*
  • Interleukin-1 / therapeutic use
  • Interleukin-18 / chemistry
  • Interleukin-18 / immunology*
  • Interleukin-18 / therapeutic use
  • Interleukin-33
  • Interleukins / immunology*
  • Interleukins / therapeutic use
  • Mice
  • Mutation
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Receptors, Interleukin-1 / immunology
  • Signal Transduction / immunology
  • Th2 Cells / immunology

Substances

  • Carrier Proteins
  • IL33 protein, human
  • Interleukin-1
  • Interleukin-18
  • Interleukin-33
  • Interleukins
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Receptors, Interleukin-1