Tansmembrane TNF-α as a novel biomarker for the diagnosis of cytokine storm in a mouse model of multiple organ failure

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-4, IL-6, IL-10, and IL-18 and it was the tmTNF-α, instead of serum TNF-α, IL-4, IL-6, IL-10, and IL-18, that reflected the 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 response 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 tmTNF-α expressed in the neutrophil could be used to diagnose CS in MOF mice, providing an experimental basis to further develop tmTNF-α for diagnosing CS patients.