Role of inflammatory mediators in angiogenesis

The angiogenic process involves several cell types and mediators, which interact to establish a specific microenvironment suitable for the formation of new capillaries from pre-existing vessels. Angiogenesis occurs in several physiological and pathological conditions, such as embryo development and wound healing, diabetic retinopathy and tumours. Inflammatory cells, namely monocytes/macrophages, T lymphocytes and neutrophils, fully participate in the angiogenic process by secreting cytokines that may affect endothelial cell (EC) functions, including EC proliferation, migration and activation. Angiogenesis is the result of a net balance between the activities exerted by positive and negative regulators. With regards to inflammatory cells and endothelium cross-talk, such balance is conceptually very similar to that of pro-inflammatory and anti-inflammatory mediators that modulate an appropriate inflammatory response. In this review we will mainly discuss the relevance of both physiological and pathological inflammatory processes in angiogenesis, with particular regards to microenvironmental contribution. We will also describe some of the most relevant pro-inflammatory cytokines in the modulation of the angiogenic process. Furthermore, we will concentrate on what has been recently reported about the mechanism by which some of these cytokines are induced during inflammation to promote a suitable microenvironment for angiogenesis and tumour progression. Pro-angiogenic cytokines, such as IL-1 and TNF, and anti-angiogenic cytokines such as IFN-gamma and IL-12, will be briefly described. We will try to provide a rationale for the use of both cytokines and cytokine blockades as novel potential pharmaceutical targets to modulate angiogenesis in chronic inflammation as well as in cancer.