INTERLEUKIN-1 RECEPTOR ANTAGONIST INHIBITS PULMONARY-HYPERTENSION INDUCED BY INFLAMMATION
INTERLEUKIN-1 RECEPTOR ANTAGONIST INHIBITS PULMONARY-HYPERTENSION INDUCED BY INFLAMMATION
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DOI：
10.1111/j.1749-6632.1994.tb39794.x
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发表时间：
1994-01-01
期刊：
影响因子：
--
通讯作者：
TUDER, R
中科院分区：
文献类型：
--
作者：
VOELKEL, NF;TUDER, R
肺血管的结构改变可以发生在血管树的每个部分，包括肺毛细血管。除了已确立的血管炎形式外，越来越多的证据表明，由细胞-细胞相互作用和介质释放定义的炎症机制是与肺动脉高压发展相关的慢性肺血管疾病的一部分。慢性阻塞性肺疾病患者和有吸烟史的患者表现出肺小动脉肌化4和由中性粒细胞、单核细胞和血小板组成的血管内细胞聚集体--可能在肺泡巨噬细胞的帮助下--这些细胞可以提供参与慢性肺动脉高压状态特征性结构改变的细胞因子和生长因子。在这项研究中，我们检验了白细胞介素-I（IL-1）在慢性肺动脉高压的发展和血管重塑过程中发挥重要作用的假设，血管重塑过程解释了高血压肺血管的结构改变。我们认为17.000道尔顿多肽。其在两种主要种类中合成，IL-γ和IL-β直接或与脂质介质组合作用于肺血管。我们的方法是在两个公认的慢性肺动脉高压实验模型中进行检查。3用白细胞介素-I受体拮抗剂（IL-1 ra）治疗是否"阻止“肺动脉高压的发展。野百合碱（MCT）大鼠模型8代表炎性肺动脉高压的范例，而慢性缺氧暴露模型代表高血压的皮下非炎性模型。y
Structural alterations of the lung vessels can occur in each part of the vascular tree including the lung capillaries. In addition to the well-established forms of angitis, there is increasing evidence that inflammatory mechanisms defined by cell-cell interactions and mediator release are part of chronic pulmonary vascular disorders associated with the development of pulmonary hypertension. Patients with chronic obstructive pulmonary diseases and patients with a smoking history demonstrate muscularization of their pulmonary small arteries4 and intravascular cell aggregates consisting of neutrophils, monocytes, and platelets-aided perhaps by alveolar macrophages-these cells could provide the cytokines and growth factors involved in the structural alterations characteristic for chronic pulmonary hypertensive states.'In this study we examine the hypothesis that interleukin-I (IL-I) play5 an important part in the development of chronic pulmonary hypertension and in the vascular remodeling process that accounts for the structural alterations of hypertensive lung vessels. We take the view that the 17.000 Dalton polypeptide. which is synthesized in two major species, IL-cy and IL-/3 acts on the lung vessels either directly or in Combination with lipid mediators. Our approach is to examine in two accepted experimental models of chronic pulmonary hypertension'. 3 whether treatment with the interleukin-I receptor antagonist (IL-lra)"~'prevents development of pulmonary hypertension. The monocrotaline (MCT) rat model8 represents the paradigm of inflammatory pulmonary hypertension, whereas the model of chronic hypoxia exposure represents a/wr sc noninflammatory model of hypertension. y