title: An expanding role for interleukin-1 blockade from gout to cancer.
abstract: There is an expanding role for interleukin (IL)-1 in diseases from gout to cancer. More than any other cytokine family, the IL-1 family is closely linked to innate inflammatory and immune responses. This linkage is because the cytoplasmic segment of all members of the IL-1 family of receptors contains a domain, which is highly homologous to the cytoplasmic domains of all toll-like receptors (TLRs). This domain, termed "toll IL-1 receptor (TIR) domain," signals as does the IL-1 receptors; therefore, inflammation due to the TLR and the IL-1 families is nearly the same. Fundamental responses such as the induction of cyclo-oxygenase type 2, increased surface expression of cellular adhesion molecules and increased gene expression of a broad number of inflammatory molecules characterizes IL-1 signal transduction as it does for TLR agonists. IL-1β is the most studied member of the IL-1 family because of its role in mediating autoinflammatory disease. However, a role for IL-1α in disease is being validated because of the availability of a neutralizing monoclonal antibody to human IL-1α. There are presently three approved therapies for blocking IL-1 activity. Anakinra is a recombinant form of the naturally occurring IL-1 receptor antagonist, which binds to the IL-1 receptor and prevents the binding of IL-1β as well as IL-1α. Rilonacept is a soluble decoy receptor that neutralizes primarily IL-1β but also IL-1α. Canakinumab is a human monoclonal antibody that neutralizes only IL-1β. Thus, a causal or significant contributing role can be established for IL-1β and IL-1α in human disease.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Colorado Denver, Aurora, Colorado, United States of America; and Department of Medicine, Radboud University, Nijmegen, the Netherlands.
authors.forename: Charles Anthony
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005334:Fever / Q000378:metabolism; D006073:Gout / Q000378:metabolism; D034381:Hearing Loss / Q000378:metabolism; D006331:Heart Diseases / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha