title: Interleukin-1 in the pathogenesis and treatment of inflammatory diseases.
abstract: More than any other cytokine family, the IL-1 family of ligands and receptors is primarily associated with acute and chronic inflammation. The cytosolic segment of each IL-1 receptor family member contains the Toll-IL-1-receptor domain. This domain is also present in each Toll-like receptor, the receptors that respond to microbial products and viruses. Since Toll-IL-1-receptor domains are functional for both receptor families, responses to the IL-1 family are fundamental to innate immunity. Of the 11 members of the IL-1 family, IL-1β has emerged as a therapeutic target for an expanding number of systemic and local inflammatory conditions called autoinflammatory diseases. For these, neutralization of IL-1β results in a rapid and sustained reduction in disease severity. Treatment for autoimmune diseases often includes immunosuppressive drugs whereas neutralization of IL-1β is mostly anti-inflammatory. Although some autoinflammatory diseases are due to gain-of-function mutations for caspase-1 activity, common diseases such as gout, type 2 diabetes, heart failure, recurrent pericarditis, rheumatoid arthritis, and smoldering myeloma also are responsive to IL-1β neutralization. This review summarizes acute and chronic inflammatory diseases that are treated by reducing IL-1β activity and proposes that disease severity is affected by the anti-inflammatory members of the IL-1 family of ligands and receptors.
authors.affiliation: Department of Medicine, University of Colorado, Aurora, CO 80045, USA. cdinarello@mac.com
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics / Q000628:therapy; D004194:Disease / Q000209:etiology / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000235:genetics / Q000628:therapy*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods*; D005810:Multigene Family; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology
chemical_list: D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors