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 angiogenesi s in adult rats was studied using the mesenteric window angiogenesis a ssay (MWAA). Murine recombinant IL-1-alpha was injected intraperitonea lly twice daily on Days 0 to 4 at 11.8 pM, 118 pM, and 1.18 nM and gro ups of animals were sacrificed on Days 7, 14, 21 and 28; controls rece ived the vehicle. Angiogenesis was quantified in terms of microvascula r spatial extension and density using technically independent. microsc opic 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, wh ereas 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 VEGF(165), bFGF, IL-8, and TNF-alpha u sing the rat MWAA and the same standardized experimental protocol, the IL-1-alpha treatment displayed a higher degree of efficacy and potenc y than that of bFGF, IL-8, and TNF-alpha. Moreover, the duration of th e 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-physiolog ic 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 clarifie d. (C) 1997 Academic Press.