An expanding role for interleukin-1 blockade from gout to cancer

被引:91
作者
Dinarello C.A. [1 ,2 ]
机构
[1] Department of Medicine, Division of Infectious Diseases, University of Colorado Denver, Aurora, CO
[2] Department of Medicine, Radboud University, Nijmegen
基金
美国国家卫生研究院;
关键词
Anakinra; Autoinflammatory Diseases; Rilonacept; Preserved Ejection Fraction Heart Failure; Neonatal-onset Multisystem Inflammatory Disease (NOMID);
D O I
10.2119/molmed.2014.00232
中图分类号
学科分类号
摘要
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. © 2014 Molecular Medicine All rights received.
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页码:S43 / S58
页数:15
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