IMMUNOSUPPRESSION IN SEPSIS DETECTED BY REACTIVATION OF LATENT VIRUSES

描述(由申请人提供)：医生越来越多地面临着脓毒症患者管理的难题。目前该领域的一个争论是，脓毒症在多大程度上主要是由于炎症失控造成的组织损伤引起的疾病，还是由于免疫抑制和未能控制入侵病原体而引起的疾病。最近的证据表明，一些脓毒症患者进入了长时间的抗炎免疫抑制阶段。这一免疫抑制阶段的特点是患者无法清除他们最初的感染和继发的医院获得性感染。 与免疫功能受损相一致的另一个败血症特征是潜伏病毒的重新激活。本方案的工作假设是，脓毒症导致免疫功能丧失，表现为多种措施，包括绝对淋巴细胞计数下降，CD4，CD8和NK细胞计数下降，导致病毒重新激活。在项目结束时，一种方法 为了确定患者何时进入脓毒症的免疫抑制阶段，将已经确定可能导致脓毒症发病的关键因素。 与公共卫生相关：在莱曼术语中，败血症是在严重感染期间发生的全身性炎症反应。仅在美国，脓毒症就导致了大约22万人死亡。虽然脓毒症通常以过度炎症开始，但如果持续下去，患者会发展成免疫受损和免疫抑制的状态。受损的免疫力可以通过多种方式表现出来，包括感染对免疫系统正常的健康个体没有特别毒力的生物体。该项目试图将患者免疫力的丧失与其他措施联系起来，包括绝对淋巴细胞计数下降和病毒重新激活。我们希望确定可用于诊断脓毒症阶段的方法，即患者是否处于过度炎症阶段或免疫受损阶段。

DESCRIPTION (provided by applicant): Physicians are increasingly confronting the difficult problem of management of patients with sepsis. A current debate in the field is the degree to which sepsis is primarily a disorder due to tissue injury from uncontrolled inflammation versus a disorder due to immunosuppression and failure to control invading pathogens. Recent evidence indicates that some patients with sepsis enter a prolonged anti-inflammatory immunosuppressive phase. This immunosuppressive phase is characterized by inability of the patient to clear their initial infection and development of secondary hospital-acquired infections. Another feature of sepsis consistent with impaired immunity is reactivation of latent viruses. The working hypothesis of the present proposal is that sepsis results in loss of immunity manifested by a variety of measures including decreased absolute lymphocyte counts, decreased CD4, CD8, and NK cell counts resulting in viral reactivation. At the conclusion of the project, a method to identify when patients enter the immunosuppressive phase of sepsis will have been identified and key factors that might contribute to sepsis pathogenesis will have been discovered. PUBLIC HEALTH RELEVANCE: In Layman Terms Sepsis is the systemic inflammatory response that occurs during severe infection. Sepsis causes approximately 220,000 deaths in the United States alone. Although sepsis typically starts as a condition with excessive inflammation, if it persists, patients develop a state of impaired immunity and immune suppression. The impaired immunity can manifest itself in many ways including infection with organisms that are not particularly virulent to healthy individuals with normal immune systems. This project seeks to relate the loss in patient immunity with other measures including decreased absolute lymphocyte counts and viral reactivation. We hope to determine methods that can be used to diagnose the stage of sepsis, i.e., whether the patient is in the excessive inflammatory phase or the impaired immunity phase.