An Expanding Role for interleukin-1 Blockade From Gout to Cancer

Mol Med. 2014 Dec 16;20 Suppl 1(Suppl 1):S43-58. doi: 10.2119/molmed.2014.00232.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / metabolism
  • Diabetes Mellitus, Type 2 / metabolism
  • Fever / metabolism
  • Gout / metabolism
  • Hearing Loss / metabolism
  • Heart Diseases / metabolism
  • Humans
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / metabolism*
  • Neoplasms / metabolism
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Interleukin-1
  • Tumor Necrosis Factor-alpha