Interleukin-8 stimulates angiogenesis in rats

To test the hypothesis that the cytokines interleukin-6 (IL-6) and IL-8 may play regulatory roles in the aberrant neovascularization in chronic inflammatory diseases, we examined their effects in a rat sponge model and compared their actions with those of IL-1 and tumor necrosis factor-alpha (TNF-alpha). Daily doses of 3 pmol IL-8, IL-1, TNF-alpha, but not IL-6, significantly accelerated the sponge-induced angiogenesis. Although lower doses (0.3 pmol) of these cytokines were inactive, IL-1 acted synergistically with subthreshold daily doses (10 pmol) of substance P (SP) and bradykinin (BK) to produce an intense angiogenic response. In contrast, IL-8 only interacted positively with IL-1, but not TNF-alpha, SP, or BK. There was no synergism or antagonism between IL-6 and SP. These results demonstrate the discrete interactions between angiogenic factors and cytokines in chronic inflammation and suggest that the sponge model is a good means for the study of such interactions.