title: IL-1, IL-18, and IL-33 families of cytokines.
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.
authors.affiliation: Division of Rheumatology, University of Colorado Denver, School of Medicine, Denver, CO, USA. william.arend@uchsc.edu
authors.forename: William P
authors.initials: WP
authors.lastname: Arend
authors.forename: Gaby
authors.initials: G
authors.lastname: Palmer
authors.forename: Cem
authors.initials: C
authors.lastname: Gabay
mesh_terms: D017398:Alternative Splicing / Q000276:immunology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007154:Immune System Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D007167:Immunotherapy; D007375:Interleukin-1 / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D020382:Interleukin-18 / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology* / Q000627:therapeutic use; D051379:Mice; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017472:Receptors, Interleukin-1 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D002352:Carrier Proteins; C506536:IL33 protein, human; D007375:Interleukin-1; D020382:Interleukin-18; D000067596:Interleukin-33; D007378:Interleukins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017472:Receptors, Interleukin-1