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-1? is the most studied member of the IL-1 family because of its role in mediating autoinflammatory disease. However, a role for IL-1? in disease is being validated because of the availability of a neutralizing monoclonal antibody to human IL-1?. 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-1? as well as IL-1?. Rilonacept is a soluble decoy receptor that neutralizes primarily IL-1? but also IL-1?. Canakinumab is a human monoclonal antibody that neutralizes only IL-1?. Thus, a causal or significant contributing role can be established for IL-1? and IL-1? in human disease.

SUBMITTER: Dinarello CA 

PROVIDER: S-EPMC4374514 | biostudies-other | 2014 Dec

REPOSITORIES: biostudies-other