The role of interleukin.6 (IL-6) and the interaction between IL-6 and interleukin-17 (IL-17) in the development of vascular inflammation and vascular dysfunction

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Vascular dysfunction, also known as functional atherosclerosis, is associated with arterial hypertension and is based on a dysbalance of the oxidative and anti-oxidative systems in the vessel system, leading to increased levels of reactive oxygen species. The activation of NADPH-oxidases by angiotensin II is essential in this process, involving cells of the immune system, especially myelomonocytic cells (monocytes, macrophages, neutrophil granulocytes) which provide the phagocytic NADPH oxidase. For recruiting these cells and for the inflammatory cell-cell-interaction, inflammatory mediators such as cytokines are important. Of the later, interleukin-6 and interleukin-17 were shown to be of crucial relevance in vascular inflammatory mechanisms that lead to vascular dysfunction. How exactly these two cytokines lead to the development of vascular dysfunction remains unclear. As these cytokines potentially could offer a new point of attack for treatment options, their roles in the development of vascular dysfunction should be further analyzed and understood.In this grant proposal, our main objective is to examine the influence of interleukin-6 on the development of vascular dysfunction while paying special attention to the Interleukin-6 and interleukin-17 interaction and their impact on the macrophage and neutrophil recruitment to the vascular wall and their vascular infiltration.