Interleukin-8 and de novo mammalian angiogenesis

In the rat mesenteric-window angiogenesis assay (MWAA), the test tissue is natively vascularized, lacks significant physiological angiogenesis and its homeostasis is unperturbed by surgical intervention. Using the rat MWAA, it is shown here that interleukin-8 (IL-8), administered at approximately physiological doses, is able to induce de novo angiogenesis. Human recombinant IL-8 was administered intraperitoneally at two daily doses of 25 pM, 250 pM and 2.5 nM for 5 consecutive days (days 0-4). Using microscopic, computer-aided techniques including image analysis, the de novo angiogenic response was quantified in groups of animals on days 7, 14 and 21 in terms of the relative vascularized area (VA), a measure of the microvascular spatial extension, and the microvascular length (MVL), a measure of microvascular density or length. The total microvascular length (TMVL) was computed from VA x MVL. A statistically significant angiogenic effect was found in terms of MVL on day 7 and in terms of VA and TMVL on day 14 following the treatment with 2.5 nM, whereas MVL was significantly increased in statistical terms on day 14 following the treatment with IL-8 at the low dose of 25 pM. Notably, IL-8 at the intermediate dose of 250 pM did not induce a statistically significant angiogenic effect in terms of VA, MVL or TMVL on any observation occasion, thereby suggesting that the dose-related angiogenic effect of IL-8 may be nonlinear. This appears to be the first paper showing that IL-8 is able to induce de novo angiogenesis in normally vascularized mammalian tissue.