Interleukin-1-alpha and de novo mammalian angiogenesis

In the literature, the role of interleukin-1 (IL-1) as an angiogen is controversial. The ability of IL-1-alpha to induce de novo angiogenesis in adult rats was studied using the mesenteric window angiogenesis assay (MWAA). Murine recombinant IL-1-alpha was injected intraperitoneally twice daily on Days 0 to 4 at 11.8 pM, 118 pM, and 1.18 nM and groups of animals were sacrificed on Days 7, 14, 21 and 28; controls received the vehicle. Angiogenesis was quantified in terms of microvascular spatial extension and density using technically independent microscopic techniques and image analysis. Compared with the vehicle control, the treatment with IL-1-alpha at doses of 118 pM and 1.18 nM induced statistically significant angiogenesis throughout the study period, whereas IL-1-alpha at 11.8 pM did not induce significant angiogenesis in statistical terms until Days 21 and 28. Compared with the previously reported angiogenic response to VEGF165, bFGF, IL-8, and TNF-alpha using the rat MWAA and the same standardized experimental protocol, the IL-1-alpha treatment displayed a higher degree of efficacy and potency than that of bFGF, IL-8, and TNF-alpha. Moreover, the duration of the significant response to IL-1-alpha exceeded that of bFGF, IL-8, and TNF-alpha. The present data indicate that IL-1-alpha at near-physiologic doses is a very effective angiogenic factor in the system used here. The response may well be multifactorially mediated, as is discussed, and the molecular mechanisms which are involved remain to be clarified.