Cuschieri Joseph, Kornblith Lucy Z, Kalthoum Hashem, Cuschieri Sophia, Pati Shibani, Piliponsky Adrian
From the Department of Surgery (J.C., L.Z.K., H.K., S.C.), University of California San Francisco, San Francisco California (S.P.), University of California San Francisco; and Department of Pediatrics (A.P.), University of Washington, Seattle, Washington.
J Trauma Acute Care Surg. 2025 Jun 3. doi: 10.1097/TA.0000000000004671.
Altered genomic expression of interferon (IFN)-γ has been demonstrated to be associated with the development of organ failure following severe injury. Altered expression of IFN-γ on innate immunity and long-term outcomes have not been previously examined. The purpose of this study was to determine the effect that IFN-γ plays on monocyte function and development of chronic critical illness (CCI).
Severely injured patients were prospectively evaluated in a development cohort (n = 124). Blood was drawn within 12 hours of injury. Plasma IFN-γ was determined by immune-assay. Clinical and outcome data were prospectively obtained for 1 year. Within this development cohort, a plasma IFN-γ level associated with CCI was determined. This IFN-γ level was analyzed within a separate prospective validation cohort (n = 78). Blood samples in this validation cohort underwent analysis for monocyte activation.
In the development cohort, an IFN-γ ≤ 50 pg/mL was associated with the development of CCI. This IFN-γ level was independently associated with CCI in the developmental cohort after adjusting for age, Injury Severity Score, lactate concentration, and blood transfusions. An IFN-γ ≤ 50 pg/mL within the validation cohort was associated with a statistically significant increase in CCI, nosocomial infection, poor discharge disposition, and 1-year mortality (25% vs. 4%, p = 0.005). Consistent with the development of CCI, attenuated IFN-γ was associated with decreased monocyte activation and surface human leukocyte antigen-DR expression.
Decreased IFN-γ is predictive of CCI development. This reduction in IFN-γ is associated with a reduction in human leukocyte antigen-DR and monocyte activation, which may result in the development of CCI, increased nosocomial infections, and poor long-term outcomes. Interferon-γ levels early following injury may be useful as a biomarker for prognosis and to serve to identify patients who could benefit from IFN-γ administration or other novel therapeutic interventions to prevent long-term complications.
Prognostic and Epidemiological; Level III.
干扰素（IFN）-γ基因组表达的改变已被证明与严重损伤后器官衰竭的发生有关。IFN-γ在固有免疫和长期预后方面表达的改变此前尚未得到研究。本研究的目的是确定IFN-γ对单核细胞功能和慢性危重病（CCI）发展的影响。
在一个发展队列（n = 124）中对严重受伤患者进行前瞻性评估。在受伤后12小时内采集血液。通过免疫测定法测定血浆IFN-γ。前瞻性获取1年的临床和预后数据。在这个发展队列中，确定与CCI相关的血浆IFN-γ水平。在一个单独的前瞻性验证队列（n = 78）中分析该IFN-γ水平。对该验证队列中的血样进行单核细胞活化分析。
在发展队列中，IFN-γ≤50 pg/mL与CCI的发生相关。在调整年龄、损伤严重程度评分、乳酸浓度和输血情况后，该IFN-γ水平在发展队列中与CCI独立相关。验证队列中IFN-γ≤50 pg/mL与CCI、医院感染、出院情况不佳和1年死亡率的统计学显著增加相关（25%对4%，p = 0.005）。与CCI的发展一致，IFN-γ减弱与单核细胞活化和表面人类白细胞抗原-DR表达降低相关。
IFN-γ降低可预测CCI的发展。这种IFN-γ的降低与人类白细胞抗原-DR和单核细胞活化的减少相关，这可能导致CCI的发展、医院感染增加和长期预后不良。受伤后早期的干扰素-γ水平可能作为预后生物标志物有用，并有助于识别可能从给予IFN-γ或其他新型治疗干预中获益以预防长期并发症的患者。
预后和流行病学；三级。
