NEUTROPHILS, CYTOKINES AND CYTOKINE RECEPTORS IN SEPTIC SHOCK

人多形核白细胞(PMNL)合成、分泌、含有 细胞因子IL-1α的特异性膜受体及其反应 以及β和肿瘤坏死因子β。这两种细胞因子和PMNL都发挥着至关重要的作用 急性播散性器官炎症在发病机制中的作用 微生物感染后可能出现的衰竭(感染性休克)。我们的目标 是为了表明人类感染性休克一直与 外周血中性粒细胞IL-1受体的扩增表达及其耐受性 这些PMNL对内毒素和IL-1α诱导IL-1β基因的表达， 而且这种表型变化在习得中起着重要作用， 严重程度，或高度致命性败血症休克的结果。本研究将：1. 确定是否也发现了脓毒症-PMNL的典型表型变化 在其他炎症病理中：a.急性播散性微生物引起 无器官衰竭的炎症；B.急性播散性炎症不 由感染引起并伴有或不伴有器官衰竭；C.局部化 没有发烧或白细胞增多的感染；D.病毒感染。2. 前瞻性研究感染性休克的高危患者 (创伤患者)来检验表型改变的假设 在脓毒症中发现-PMNL与脓毒症的风险、严重程度或结局相关 令人震惊。3.检验增加受体蛋白合成的假说 IL-1R在脓毒症-PMNL上的表达增加 评估转录和翻译过程。4.确定 脓毒症-PMNL对IL-1β基因的适应位点 表情。我们的发现应该会提供对细胞事件的洞察 调节人类对严重炎症的反应，并产生影响 感染性休克的风险、预后和治疗。

Human polymorphonuclear leukocytes (PMNL) synthesize, secrete, contain specific membrane receptors for, and respond to the cytokines IL-1 alpha and beta and TNF beta. Both of these cytokines and PMNL play an essential role in the pathogenesis of acute disseminated inflammation with organ failure which may follow microbial infection (septic shock). Our objective is to show that septic shock in humans is consistently associated with amplified expression of receptors for IL-1 on blood PMNL, and tolerance of these PMNL to LPS- and IL-1 alpha-induced expression of the IL-1 beta gene, and that such phenotypic changes play an important role in acquisition, severity, or outcome of highly lethal septic shock. This research will: 1. Determine if the phenotypic changes typical of sepsis-PMNL are also found in other inflammatory pathologies: A. acute disseminated microbial-induced inflammation without organ failure; B. acute disseminated inflammation not caused by infection and with or without organ failure; C. localized infection without fever or leukocytosis; D. viral infection. 2. Prospectively study patients at high risk for developing septic shock (trauma-patients) to test the hypothesis that the phenotypic alterations found in sepsis-PMNL correlate with risk, severity, or outcome of septic shock. 3. Test the hypothesis that increased synthesis of receptor protein is responsible for increased expression of IL-1 R on sepsis-PMNL by evaluating transcriptional and translational processes. 4. Determine the site responsible for the adaptation of sepsis-PMNL to IL-1 beta gene expression. Our findings should provide insight into cellular events which regulate the human response to severe inflammation, and have implications for risk, prognosis, and therapy of septic shock.