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| Content Provider | PubMed Central |
|---|---|
| Author | Dinarello, Charles A. |
| Abstract | The clinical successes of targeting angiogenesis provide a basis for trials of interleukin-1 (IL-1) blockade and particularly anti-IL-1β 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-1β, 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-1β 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-1β 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. |
| Related Links | http://dx.doi.org/10.1007/s10555-010-9229-0 |
| Ending Page | 329 |
| Page Count | 13 |
| Starting Page | 317 |
| File Format | |
| ISSN | 01677659 |
| e-ISSN | 15737233 |
| Journal | Cancer Metastasis Reviews |
| Issue Number | 2 |
| Volume Number | 29 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2010-06-01 |
| Access Restriction | Open |
| Rights Holder | Springer US |
| Subject Keyword | Cancer Research Oncology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |
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