Qu Hui-Qi, Snyder James, Connolly John, Glessner Joseph, Kao Charlly, Sleiman Patrick, Hakonarson Hakon
The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Biomedicines. 2022 Jan 25;10(2):264. doi: 10.3390/biomedicines10020264.
The novel therapeutic target cytokine LIGHT (TNFSF14) was recently shown to play a major role in COVID-19-induced acute respiratory distress syndrome (ARDS). This study aims to investigate the associations of plasma LIGHT and another potentially targetable cytokine, interleukin-18 (IL-18), with ARDS, acute hypoxic respiratory failure (AHRF), or acute kidney injury (AKI), caused by non-COVID-19 viral or bacterial sepsis. A total of 280 subjects diagnosed with sepsis, including 91 cases with sepsis triggered by viral infections, were investigated in this cohort study. Day 0 plasma LIGHT and IL-18, as well as 59 other biomarkers (cytokines, chemokines, and acute-phase reactants) were measured by sensitive bead immunoassay and associated with symptom severity. We observed significantly increased LIGHT level in both bacterial sepsis patients ( = 1.80 × 10) and patients with sepsis from viral infections ( = 1.78 × 10). In bacterial sepsis, increased LIGHT level was associated with ARDS, AKI, and higher Apache III scores, findings also supported by correlations of LIGHT with other biomarkers of organ failure. IL-18 levels were highly variable across individuals and consistently correlated with Apache III scores, mortality, and AKI in both bacterial and viral sepsis. There was no correlation between LIGHT and IL-18. For the first time, we demonstrate independent effects of LIGHT and IL-18 in septic organ failure. The association of plasma LIGHT with AHRF suggests that targeting the pathway warrants exploration, and ongoing trials may soon elucidate whether this is beneficial. Given the large variance of plasma IL-18 among septic subjects, targeting this pathway requires precise application.
新型治疗靶点细胞因子LIGHT（TNFSF14）最近被证明在新冠病毒诱导的急性呼吸窘迫综合征（ARDS）中起主要作用。本研究旨在调查血浆LIGHT和另一种潜在可靶向的细胞因子白细胞介素-18（IL-18）与非新冠病毒感染的病毒或细菌性脓毒症所致的ARDS、急性低氧性呼吸衰竭（AHRF）或急性肾损伤（AKI）之间的关联。在这项队列研究中，共调查了280名被诊断为脓毒症的受试者，其中包括91例由病毒感染引发脓毒症的病例。通过灵敏的微珠免疫测定法测量了第0天的血浆LIGHT和IL-18，以及其他59种生物标志物（细胞因子、趋化因子和急性期反应物），并将其与症状严重程度相关联。我们观察到细菌性脓毒症患者（ = 1.80 × 10）和病毒感染所致脓毒症患者（ = 1.78 ×
10）的LIGHT水平均显著升高。在细菌性脓毒症中，LIGHT水平升高与ARDS、AKI以及更高的急性生理学及慢性健康状况评分系统III（Apache III）评分相关，LIGHT与其他器官衰竭生物标志物的相关性也支持了这些发现。IL-18水平在个体间差异很大，并且在细菌性和病毒性脓毒症中均与Apache III评分、死亡率和AKI持续相关。LIGHT和IL-18之间无相关性。我们首次证明了LIGHT和IL-18在脓毒症性器官衰竭中的独立作用。血浆LIGHT与AHRF的关联表明，靶向该途径值得探索，正在进行的试验可能很快会阐明这是否有益。鉴于脓毒症受试者血浆IL-18差异很大，靶向该途径需要精确应用。
