Role of IL-1-mediated inflammation in tumor angiogenesis.

Angiogenesis, or generation of new blood vessels from pre-existing vessels, is an integral part of many physiological or pathological processes, including tumor growth. Physiological angiogenesis is a complex process controlled by different proangiogenic as well as antiangiogenic factors. For angiogenic induction, the balance between these pro- and antiangiogenic factors in the microenvironment has to shift in favor of proangiogenic factors, either by upregulation of these pro-angiogenic factors or by downregulation of angiogenic inhibitors. Proinflammatory cytokines, such as IL-1 and TNFa, were found to be major proangiogenic stimuli of both physiological and pathological angiogenesis. The IL-1 family consists of pleiotropic proinflammatory and immunoregulatory cytokines, namely, IL-1alpha and IL-1beta, and one antagonistic protein, the IL-1 receptor antagonist (IL-1Ra), which binds to IL-1 receptors without transmitting an activation signal and represents a physiological inhibitor of preformed IL-1. Previously, we described an important role for microenvironment IL-1, mainly IL-1beta, in tumor angiogenesis. In this chapter, we analyze the role of microenvironment host- and tumor cell-derived IL-1 on angiogenesis and the role of inflammation in pathological angiogenesis.