Department of Clinical Laboratory, The Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China.
Inflammation. 2023 Feb;46(1):359-369. doi: 10.1007/s10753-022-01738-6. Epub 2022 Sep 14.
A cytokine storm (CS) is an out-of-control inflammatory response closely associated with the progression of diseases, such as multiple organ failure (MOF), severe sepsis, and severe or critical COVID-19. However, there is currently a lack of reliable diagnostic markers to distinguish CS from normal inflammatory responses. Tumor necrosis factor-α (TNF-α) includes transmembrane TNF-α (tmTNF-α) and secreted TNF-α (sTNF-α). The MOF mouse model in this study showed that the tmTNF-α expression changes in the neutrophils differed from the serum TNF-α and serum IL-18, INF-γ, IL-4, and IL-6. Furthermore, tmTNF-α, instead of serum TNF-α, IL-18, INF-γ, IL-4, and IL-6, reflected liver and kidney tissue damage and increased with the aggravation of these injuries. Analysis of the ROC results showed that tmTNF-α effectively distinguished between inflammatory responses and CS and efficiently differentiated between surviving and dead mice. It also significantly improved the diagnostic value of the traditional CRP marker for CS. These results indicated that the tmTNF-α expressed in the neutrophils could be used to diagnose CS in MOF mice, providing an experimental basis to further develop tmTNF-α for diagnosing CS patients.
细胞因子风暴（CS）是一种失控的炎症反应，与多种疾病的进展密切相关，如多器官衰竭（MOF）、严重败血症和严重或危急的 COVID-19。然而，目前缺乏可靠的诊断标志物来区分 CS 与正常炎症反应。肿瘤坏死因子-α（TNF-α）包括跨膜 TNF-α（tmTNF-α）和分泌型 TNF-α（sTNF-α）。本研究中的 MOF 小鼠模型表明，中性粒细胞中 tmTNF-α的表达变化与血清 TNF-α和血清 IL-18、INF-γ、IL-4 和 IL-6 不同。此外，tmTNF-α而不是血清 TNF-α、IL-18、INF-γ、IL-4 和 IL-6，反映了肝和肾组织损伤，并随着这些损伤的加重而增加。ROC 结果分析表明，tmTNF-α有效地将炎症反应与 CS 区分开来，并能有效区分存活和死亡的小鼠。它还显著提高了传统 CRP 标志物对 CS 的诊断价值。这些结果表明，中性粒细胞中表达的 tmTNF-α可用于诊断 MOF 小鼠中的 CS，为进一步开发 tmTNF-α诊断 CS 患者提供了实验依据。
