Iinterleukin-1 (IL-1) is a proinflammatory cytokine with various immune, degradative, and growth promoting roles. There are two IL-1 agonistic proteins — IL-1β and IL-1α — and one antagonistic protein, the IL-1 receptor antagonist IL-1Ra — commercially produced as anakinra and used in the treatment of rheumatoid arthritis. However, the roles of endogenous IL-1 in mediating in vivo tumor growth and angiogenesis have been unclear. In the February 18 Proceedings of the National Academy of Sciences, Elena Voronov and colleagues at the Ben-Gurion University of the Negev, Beer-Sheva, Israel, show that microenvironmental IL-1β and, to a lesser extent, IL-1α are required for in vivo angiogenesis and invasiveness for certain tumor cells (PNAS, DOI:10.1073/pnas.0437939100, February 18, 2003).

Voronov et al. used IL-1β and IL-1α knockout mice. They observed that various types of tumor cell — including B16 melanoma cells — failed to develop into local tumors in IL-1β deficient mice, and to a lesser degree in IL-1 α-deficient animals. In addition, IL-1β^-/- mice failed to initiate angiogenesis in a subcutaneous Matrigel plug containing B16 cells. The angiogenic response was partially restored upon the addition of exogenous IL-1 and blocked in wild type mice by the IL-1 receptor antagonist IL-1Ra.

"Thus, the use of IL-1Ra, which blocks cell activation by either IL-1β or IL-1α and is approved for reducing inflammation in patients with rheumatoid arthritis, may be an appropriate therapeutic strategy for inhibiting tumor angiogenesis," conclude the authors.