title: Interleukin-1β in innate inflammation, autophagy and immunity.
abstract: Although IL-1β is the master inflammatory cytokine in the IL-1 family, after more than ten years of continuous breeding, mice deficient in IL-1β exhibit no spontaneous disease. Therefore, one concludes that IL-1β is not needed for homeostasis. However, IL-1β-deficient mice are protected against local and systemic inflammation due to live infections, autoimmune processes, tumor metastasis and even chemical carcinogenesis. Based on a large number of preclinical studies, blocking IL-1β activity in humans with a broad spectrum of inflammatory conditions has reduced disease severity and for many, has lifted the burden of disease. Rare and common diseases are controlled by blocking IL-1β. Immunologically, IL-1β is a natural adjuvant for responses to antigen. Alone, IL-1β is not a growth factor for lymphocytes; rather in antigen activated immunocompetent cells, blocking IL-1 reduces IL-17 production. IL-1β markedly increases in the expansion of naive and memory CD4T cells in response to challenge with their cognate antigen. The response occurs when only specific CD4T cells respond to IL-1β and not to IL-6 or CD-28. A role for autophagy in production of IL-1β has emerged with deletion of the autophagy gene ATG16L1. Macrophages from ATG16L1-deficient mice produce higher levels of IL-1β after stimulation with TLR4 ligands via a mechanism of caspase-1 activation. The implications for increased IL-1β release in persons with defective autophagy may have clinical importance for disease.
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Medicine, University of Colorado Denver, Aurora, CO, USA. Electronic address: cdinare333@aol.com.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001343:Autophagy / Q000276:immunology*; D000071183:Autophagy-Related Proteins; D018106:CD28 Antigens / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics; D020170:Caspase 1 / Q000096:biosynthesis / Q000276:immunology; D056587:Cryopyrin-Associated Periodic Syndromes / Q000235:genetics / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D051379:Mice; D009362:Neoplasm Metastasis / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology; D017382:Reactive Oxygen Species; D058486:Receptors, Purinergic P2X7 / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D051197:Toll-Like Receptor 4
chemical_list: C532820:Atg16l1 protein, mouse; D000071183:Autophagy-Related Proteins; D018106:CD28 Antigens; D002352:Carrier Proteins; C508600:IL6 protein, human; D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D058486:Receptors, Purinergic P2X7; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D020170:Caspase 1
keywords: Autophagy; Caspase-1-independent; Innate inflammation; Interleukin-1β