Host response to post-operative pneumonia

描述（来自申请人摘要的逐字记录）：麻醉/手术 使患者易患医院获得性肺炎的机制， 没有完全定义。病毒性呼吸道感染的存在 (RTI)在麻醉/手术期间， 反应我们实验室的证据表明麻醉/手术 诱导细胞因子应答的变化（例如，TNF α、MIP-2、IFN γ）， 白细胞募集和流感RTI的肺损伤。这些响应是 也是宿主对细菌病原体的先天防御的关键。我们的重点是 研究病毒RTI期间使宿主易患 术后细菌性肺炎我们假设麻醉/手术将 在一个过程中的不同时期， 通过改变前和后细胞因子的表达， 从而降低抗菌防御。目标#1将评估 流感期间麻醉/手术对细菌清除、炎症细胞 内流和细胞因子表达。我们预测 流感期间的剖腹手术将促进MCP-1的相对表达， IL-10超过TNF α、MIP-2和IFN γ。目标#2：将离体评估 剖腹手术和流感对a）LPS刺激的aMphi细胞因子的联合作用 表达和吞噬活性，和B）体外抗MCP-1的能力， 抗IL-10或IFN γ给药以改善M功能障碍。我们推测 流感期间的剖腹手术会改变aMphi的调节功能， 由于选择性增强表达而降低效应子功能 与促炎细胞因子相比，最后，在目标#3中，我们将检查 内源性细胞因子在抑制抗菌药物中的作用 选择性细胞因子介导的流感期间剖腹手术后的防御 操纵细菌清除、炎性细胞流入和细胞因子 水平将被评估。我们预期IL-10或MCP-1的中和， 给予IFN γ或增加TNF α表达将改善 剖腹手术后的抗菌宿主防御， 流感。这些研究将检查导致改变的机制， 病毒性RTI后手术后的细菌清除，评估 手术后肺炎的发病机制，并建议免疫佐剂 预防这种并发症的策略。

DESCRIPTION (Verbatim from the Applicant's Abstract): Anesthesia/surgery predisposes the patient to develop nosocomial pneumonia by mechanisms that are not completely defined. The presence of a viral respiratory tract infection (RTI) during anesthesia/surgery further complicates the host antibacterial response. Evidence from our laboratory has demonstrated anesthesia/surgery induces changes in cytokine response (e.g., TNFalpha, MIP-2, IFNgamma), leukocyte recruitment, and lung injury to influenza RTI. These responses are also critical to innate host defenses against bacterial pathogens. Our focus is to examine cellular mechanisms during a viral RTI that predispose the host to a post-surgical bacterial pneumonia. We hypothesize that anesthesia/surgery will change host responses differently during distinct periods in the course of a viral RTI by altering expression of pro- and antiinflammatory cytokines, thereby decreasing antibacterial defenses. Aim #1 will assess the effects of anesthesia/surgery during influenza on bacterial clearance, inflammatory cell influx, and cytokine expression an Escherichia coli challenge. We predict that laparotomy during influenza will promote the relative expression of MCP-1 and IL-10 over TNFalpha, MIP-2, and IFNgamma. Aim #2: will assess ex vivo the combined effect of laparotomy and influenza on a) LPS stimulated aMphi cytokine expression and phagocytic activity, and b) the ability of in vitro antiMCP-1, antiIL-10, or IFNgamma administration to improve M dysfunction. We postulate that laparotomy during influenza will alter aMphi regulatory functions and decrease effector functions as a result of selective enhancement of expression anti-compared to proinflammatory cytokines. Finally, in Aim #3, we will examine the contribution of endogenous cytokines in the suppression of antibacterial defenses following laparotomy during influenza by selective cytokine manipulations. Bacterial clearance, inflammatory cell influx, and cytokine levels will be assessed. We anticipate that neutralization of IL-10 or MCP-1, administration of IFNgamma, or increased TNFalphaexpression will improve antibacterial host defenses following laparotomy during physical signs of influenza. These studies will examine mechanisms that lead to alterations in bacterial clearance post-surgically following a viral RTI, assess the pathogenesis of post-surgical pneumonia in general, and suggest immune adjuvant strategies to prevent this complication.