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PMID: 20422276 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Why not treat human cancer with interleukin-1 blockade?

Cancer metastasis reviews ·Vol. 29 ·No. 2 ·2010-06-00 ·Pages 317-29

Dinarello CA

Abstract

The clinical successes of targeting angiogenesis provide a basis for trials of interleukin-1 (IL-1) blockade and particularly anti-IL-1beta as an add-on therapy in human metastatic disease. In animal studies for over 20 years, IL-1 has been demonstrated to increase adherence of tumor cells to the endothelium in vitro, and administration of IL-1 to mice increases the number of metastatic colonies and tumor growth. Importantly, reducing endogenous IL-1 activity, particularly IL-1beta, with the naturally occurring IL-1 receptor antagonist (IL-1Ra) reduces both metastasis as well as tumor burden. Inhibition of IL-1 activity prevents in vivo blood vessel formation induced by products released from hypoxic macrophages or vascular endothelial cell growth factor itself. Mice deficient in IL-1beta do not form blood vessels in matrigels embedded with vascular endothelial cell growth factor or containing products of macrophages. Recombinant IL-1Ra (anakinra) has been administered to over 1,000 patients with septic shock resulting in a consistent reduction in all-cause 28-day mortality. Approved for treatment of rheumatoid arthritis, anakinra has a remarkable safety record. Anakinra resulted in decreased blood vessels in the pannus of affected joints in patients with rheumatoid arthritis. Neutralizing monoclonal antibodies to IL-1beta and a soluble receptor to IL-1 are approved for treating chronic inflammatory diseases. Given the availability of three therapeutic agents for limiting IL-1 activity, the safety of blocking IL-1, and the clear benefit of blocking IL-1 activity in animal models of metastasis and angiogenesis, clinical trials of IL-1 blockade should be initiated, particularly as an add-on therapy of patients receiving antiangiogenesis-based therapies.

MeSH Terms
Angiogenesis Inhibitors/therapeutic use Animals Antineoplastic Agents/therapeutic use Antirheumatic Agents/therapeutic use Arthritis, Rheumatoid/drug therapy Humans Interleukin 1 Receptor Antagonist Protein/metabolism,therapeutic use Interleukin-1/antagonists & inhibitors Neoplasms/blood supply,drug therapy Neovascularization, Pathologic/drug therapy
Chemicals
Angiogenesis Inhibitors Antineoplastic Agents Antirheumatic Agents Interleukin 1 Receptor Antagonist Protein Interleukin-1
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Dinarello Charles A
Department of Medicine, University of Colorado, 12700 East 19th Ave., B168, Aurora, CO 80045, USA. [email protected]
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Article Info
Journal
Cancer metastasis reviews
Abbr.
Cancer Metastasis Rev
ISSN
1573-7233
DOI
10.1007/s10555-010-9229-0
Email
[email protected]
Published
2010-06-00
Pages
317-29
Language
English
Region
Netherlands
NLM ID
8605731
PMCID
PMC2865633
Subset
IM
Grants
NIAID NIH HHS · R01 AI015614 · United States
NIAID NIH HHS · R56 AI015614 · United States
NIAID NIH HHS · AI15614 · United States
External Links
PubMed source DOI: 10.1007/s10555-010-9229-0 PMC Full Text View journal details
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