PDF(Pubmed)
Abstract：
OBJECTIVE: While cytokine response patterns are pivotal in mediating immune responses, they are also often dysregulated in sepsis and critical illness. We hypothesized that these immunological deficits, quantifiable through ex vivo whole blood stimulation assays, may be indicative of subsequent organ dysfunction.
METHODS: In a prospective observational study, adult septic patients and critically ill but nonseptic controls were identified within 48 hours of critical illness onset. Using a rapid, ex vivo assay based on responses to lipopolysaccharide (LPS), anti-CD3/anti-CD28 antibodies, and phorbol 12-myristate 13-acetate with ionomycin, cytokine responses to immune stimulants were quantified. The primary outcome was the relationship between early cytokine production and subsequent organ dysfunction, as measured by the Sequential Organ Failure Assessment score on day 3 of illness (SOFAd3).
METHODS: Patients were recruited in an academic medical center and data processing and analysis were done in an academic laboratory setting.
METHODS: Ninety-six adult septic and critically ill nonseptic patients were enrolled.
METHODS: None.
RESULTS: Elevated levels of tumor necrosis factor and interleukin-6 post-endotoxin challenge were inversely correlated with SOFAd3. Interferon-gamma production per lymphocyte was inversely related to organ dysfunction at day 3 and differed between septic and nonseptic patients. Clustering analysis revealed two distinct immune phenotypes, represented by differential responses to 18 hours of LPS stimulation and 4 hours of anti-CD3/anti-CD28 stimulation.
CONCLUSIONS: Our rapid immune profiling technique offers a promising tool for early prediction and management of organ dysfunction in critically ill patients. This information could be pivotal for early intervention and for preventing irreversible organ damage during the acute phase of critical illness.
METHODS: In a prospective observational study, adult septic patients and critically ill but nonseptic controls were identified within 48 hours of critical illness onset. Using a rapid, ex vivo assay based on responses to lipopolysaccharide (LPS), anti-CD3/anti-CD28 antibodies, and phorbol 12-myristate 13-acetate with ionomycin, cytokine responses to immune stimulants were quantified. The primary outcome was the relationship between early cytokine production and subsequent organ dysfunction, as measured by the Sequential Organ Failure Assessment score on day 3 of illness (SOFAd3).
METHODS: Patients were recruited in an academic medical center and data processing and analysis were done in an academic laboratory setting.
METHODS: Ninety-six adult septic and critically ill nonseptic patients were enrolled.
METHODS: None.
RESULTS: Elevated levels of tumor necrosis factor and interleukin-6 post-endotoxin challenge were inversely correlated with SOFAd3. Interferon-gamma production per lymphocyte was inversely related to organ dysfunction at day 3 and differed between septic and nonseptic patients. Clustering analysis revealed two distinct immune phenotypes, represented by differential responses to 18 hours of LPS stimulation and 4 hours of anti-CD3/anti-CD28 stimulation.
CONCLUSIONS: Our rapid immune profiling technique offers a promising tool for early prediction and management of organ dysfunction in critically ill patients. This information could be pivotal for early intervention and for preventing irreversible organ damage during the acute phase of critical illness.
摘要：
目的：虽然细胞因子应答模式在介导免疫应答中起关键作用，在败血症和危重疾病中，它们也经常失调。我们假设这些免疫缺陷，通过离体全血刺激测定可量化，可能指示随后的器官功能障碍。
方法：在一项前瞻性观察研究中，在危重病发病48小时内发现了成人败血症患者和危重但非败血症的对照.使用快速，基于对脂多糖（LPS）的反应的离体测定，抗CD3/抗CD28抗体，和佛波醇12-肉豆蔻酸盐13-乙酸酯与离子霉素，定量细胞因子对免疫刺激剂的反应。主要结果是早期细胞因子产生与随后的器官功能障碍之间的关系，根据疾病第3天的序贯器官衰竭评估评分（SOFAd3）进行测量。
方法：在学术医学中心招募患者，并在学术实验室环境中进行数据处理和分析。
方法：纳入96例成人败血症和危重非败血症患者。
方法：无。
结果：内毒素攻击后肿瘤坏死因子和白细胞介素-6水平升高与SOFAd3呈负相关。每个淋巴细胞产生的干扰素-γ与第3天的器官功能障碍成反比，并且在败血症和非败血症患者之间存在差异。聚类分析揭示了两种不同的免疫表型，由对18小时的LPS刺激和4小时的抗CD3/抗CD28刺激的差异反应表示。
结论：我们的快速免疫分析技术为危重患者器官功能障碍的早期预测和治疗提供了一个有前景的工具。这些信息对于早期干预和预防危重病急性期不可逆的器官损伤至关重要。
方法：在一项前瞻性观察研究中，在危重病发病48小时内发现了成人败血症患者和危重但非败血症的对照.使用快速，基于对脂多糖（LPS）的反应的离体测定，抗CD3/抗CD28抗体，和佛波醇12-肉豆蔻酸盐13-乙酸酯与离子霉素，定量细胞因子对免疫刺激剂的反应。主要结果是早期细胞因子产生与随后的器官功能障碍之间的关系，根据疾病第3天的序贯器官衰竭评估评分（SOFAd3）进行测量。
方法：在学术医学中心招募患者，并在学术实验室环境中进行数据处理和分析。
方法：纳入96例成人败血症和危重非败血症患者。
方法：无。
结果：内毒素攻击后肿瘤坏死因子和白细胞介素-6水平升高与SOFAd3呈负相关。每个淋巴细胞产生的干扰素-γ与第3天的器官功能障碍成反比，并且在败血症和非败血症患者之间存在差异。聚类分析揭示了两种不同的免疫表型，由对18小时的LPS刺激和4小时的抗CD3/抗CD28刺激的差异反应表示。
结论：我们的快速免疫分析技术为危重患者器官功能障碍的早期预测和治疗提供了一个有前景的工具。这些信息对于早期干预和预防危重病急性期不可逆的器官损伤至关重要。
