Samuelsen Abigail, Lehman Erik, Burrows Parker, Bonavia Anthony S
Department of Anesthesiology and Perioperative Medicine, Penn State Medical Center, Hershey, PA, United States.
Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, United States.
Front Immunol. 2024 Dec 6;15:1498974. doi: 10.3389/fimmu.2024.1498974. eCollection 2024.
Immunoparalysis is a state of immune dysfunction characterized by a marked reduction in the immune system's responsiveness, often observed following severe infections, trauma, or critical illness. This study aimed to perform a longitudinal assessment of immune function over the initial two weeks following the onset of sepsis and critical illness.
We compared ex vivo-stimulated cytokine release from whole blood of critically ill patients to traditional markers of immunoparalysis, including monocyte Human Leukocyte Antigen (mHLA)-DR expression and absolute lymphocyte count (ALC). A total of 64 critically ill patients were recruited in a tertiary care academic medical setting, including 31 septic and 33 non-septic patients.
While mHLA-DR expression significantly increased over time, this was primarily driven by the non-septic subset of critically ill patients. ALC recovery was more pronounced in septic patients. Ex vivo stimulation of blood from septic patients revealed significant increases in TNF and IL-6 production over time. However, interferon-gamma production varied depending on the ex vivo stimulant used, and after normalization of cytokine concentrations to lymphocyte counts, it did not show significant recovery over time from illness onset. No significant correlation was found between mHLA-DR expression and other immunoparalysis biomarkers.
These findings suggest the need for more nuanced immune monitoring approaches beyond the traditional 'sepsis' versus 'non-sepsis' classifications in critically ill patients. Additionally, they provide further evidence of a potential window for targeted immunotherapy in the first weeks of critical illness.
免疫麻痹是一种免疫功能障碍状态，其特征是免疫系统反应性显著降低，常在严重感染、创伤或危重病后出现。本研究旨在对脓毒症和危重病发作后的最初两周内的免疫功能进行纵向评估。
我们将危重病患者全血经体外刺激后的细胞因子释放与免疫麻痹的传统标志物进行比较，包括单核细胞人类白细胞抗原（mHLA）-DR表达和绝对淋巴细胞计数（ALC）。在一家三级医疗学术机构招募了64名危重病患者，包括31名脓毒症患者和33名非脓毒症患者。
虽然mHLA-DR表达随时间显著增加，但这主要由危重病患者的非脓毒症亚组驱动。脓毒症患者的ALC恢复更为明显。对脓毒症患者的血液进行体外刺激显示，TNF和IL-6的产生随时间显著增加。然而，γ干扰素的产生因所用的体外刺激剂而异，并且在将细胞因子浓度标准化为淋巴细胞计数后，从疾病发作开始随时间未显示出显著恢复。未发现mHLA-DR表达与其他免疫麻痹生物标志物之间存在显著相关性。
这些发现表明，对于危重病患者，需要超越传统的“脓毒症”与“非脓毒症”分类的更细致的免疫监测方法。此外，它们为危重病最初几周内进行靶向免疫治疗的潜在窗口期提供了进一步证据。
