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

血管功能障碍，也被称为功能性动脉粥样硬化，与动脉高血压有关，是基于血管系统中氧化和抗氧化系统的失衡，导致活性氧水平升高。在这个过程中，血管紧张素II激活NADPH氧化酶是必不可少的，涉及免疫系统的细胞，特别是提供吞噬NADPH氧化酶的骨髓单核细胞（单核细胞、巨噬细胞、中性粒细胞）。对于募集这些细胞和炎症细胞之间的相互作用，炎症介质如细胞因子是重要的。在后者中，白细胞介素-6和白细胞介素-17被证明在导致血管功能障碍的血管炎症机制中具有至关重要的相关性。这两种细胞因子究竟如何导致血管功能障碍尚不清楚。由于这些细胞因子可能为治疗方案提供新的攻击点，它们在血管功能障碍发展中的作用应该进一步分析和理解。在本次拨款申请中，我们的主要目的是研究白细胞介素-6对血管功能障碍发展的影响，同时特别关注白细胞介素-6和白细胞介素-17的相互作用及其对巨噬细胞和中性粒细胞向血管壁募集及其血管浸润的影响。

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.