Penn State Department of Anesthesiology and Perioperative Medicine, Hershey, PA.
Division of Critical Care Medicine, Department of Pediatrics, Penn State Milton S. Hershey Medical Center, Hershey, PA.
Crit Care Explor. 2024 Jun 25;6(7):e1106. doi: 10.1097/CCE.0000000000001106. eCollection 2024 Jul 1.
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.
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).
Patients were recruited in an academic medical center and data processing and analysis were done in an academic laboratory setting.
Ninety-six adult septic and critically ill nonseptic patients were enrolled.
None.
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.
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.
细胞因子反应模式在介导免疫反应中起着关键作用，但在脓毒症和危重病中也经常失调。我们假设，这些通过体外全血刺激试验可量化的免疫缺陷可能表明随后发生器官功能障碍。
在一项前瞻性观察性研究中，在危重病发病后 48 小时内确定成年脓毒症患者和危重病但非脓毒症对照患者。使用基于脂多糖（LPS）、抗 CD3/抗 CD28 抗体和佛波醇 12-肉豆蔻酸 13-乙酸酯与离子霉素反应的快速体外测定法，定量细胞因子对免疫刺激物的反应。主要结局是早期细胞因子产生与疾病第 3 天（SOFAd3）的序贯器官衰竭评估评分（SOFA）所测后续器官功能障碍之间的关系。
在学术医疗中心招募患者，在学术实验室环境中进行数据处理和分析。
纳入 96 例成年脓毒症和危重病非脓毒症患者。
无。
内毒素挑战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 天的器官功能障碍呈负相关，且在脓毒症和非脓毒症患者之间存在差异。聚类分析显示两种不同的免疫表型，代表对 18 小时 LPS 刺激和 4 小时抗 CD3/抗 CD28 刺激的不同反应。
我们的快速免疫分析技术为危重病患者器官功能障碍的早期预测和管理提供了有前途的工具。这些信息对于早期干预和防止危重病急性期的不可逆器官损伤至关重要。
