PMID- 36104516 OWN - NLM STAT- MEDLINE DCOM- 20230301 LR - 20230301 IS - 1573-2576 (Electronic) IS - 0360-3997 (Print) IS - 0360-3997 (Linking) VI - 46 IP - 1 DP - 2023 Feb TI - Transmembrane TNF-alpha as a Novel Biomarker for the Diagnosis of Cytokine Storms in a Mouse Model of Multiple Organ Failure. PG - 359-369 LID - 10.1007/s10753-022-01738-6 [doi] AB - 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-alpha (TNF-alpha) includes transmembrane TNF-alpha (tmTNF-alpha) and secreted TNF-alpha (sTNF-alpha). The MOF mouse model in this study showed that the tmTNF-alpha expression changes in the neutrophils differed from the serum TNF-alpha and serum IL-18, INF-gamma, IL-4, and IL-6. Furthermore, tmTNF-alpha, instead of serum TNF-alpha, IL-18, INF-gamma, 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-alpha 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-alpha expressed in the neutrophils could be used to diagnose CS in MOF mice, providing an experimental basis to further develop tmTNF-alpha for diagnosing CS patients. CI - (c) 2022. The Author(s). FAU - Yang, Peng AU - Yang P AD - Department of Clinical Laboratory, The Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China. FAU - Zeng, Yimin AU - Zeng Y AD - Department of Clinical Laboratory, The Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China. FAU - Yang, Fang AU - Yang F AD - Department of Clinical Laboratory, The Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China. FAU - Peng, Xin AU - Peng X AD - Department of Clinical Laboratory, The Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China. FAU - Hu, Yongsheng AU - Hu Y AD - Department of Clinical Laboratory, The Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China. FAU - Tan, Xuhong AU - Tan X AD - Department of Clinical Laboratory, The Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China. FAU - Zhang, Ruping AU - Zhang R AD - Department of Clinical Laboratory, The Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China. 468050863@qq.com. LA - eng PT - Journal Article DEP - 20220914 PL - United States TA - Inflammation JT - Inflammation JID - 7600105 RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Interleukin-6) RN - 0 (Receptors, Tumor Necrosis Factor, Type I) RN - 0 (Interleukin-18) RN - 207137-56-2 (Interleukin-4) RN - 0 (Biomarkers) SB - IM MH - Animals MH - Mice MH - *Tumor Necrosis Factor-alpha/metabolism MH - Interleukin-6/metabolism MH - Receptors, Tumor Necrosis Factor, Type I/metabolism MH - Interleukin-18 MH - Multiple Organ Failure/diagnosis MH - Interleukin-4 MH - Cytokine Release Syndrome MH - *COVID-19 MH - Biomarkers MH - COVID-19 Testing PMC - PMC9473472 OTO - NOTNLM OT - Cytokine storm OT - Diagnostic marker OT - Inflammatory responses OT - Multiple organ failure OT - Transmembrane TNF-alpha COIS- The authors declare no competing interests. EDAT- 2022/09/15 06:00 MHDA- 2023/03/03 06:00 PMCR- 2022/09/14 CRDT- 2022/09/14 23:31 PHST- 2022/06/15 00:00 [received] PHST- 2022/09/08 00:00 [accepted] PHST- 2022/09/08 00:00 [revised] PHST- 2022/09/15 06:00 [pubmed] PHST- 2023/03/03 06:00 [medline] PHST- 2022/09/14 23:31 [entrez] PHST- 2022/09/14 00:00 [pmc-release] AID - 10.1007/s10753-022-01738-6 [pii] AID - 1738 [pii] AID - 10.1007/s10753-022-01738-6 [doi] PST - ppublish SO - Inflammation. 2023 Feb;46(1):359-369. doi: 10.1007/s10753-022-01738-6. Epub 2022 Sep 14.