Susceptibility-Related Cytokine Panel for Prediction of Polygonum multiflorum-Induced Hepatotoxicity in Humans

Can Tu,1,2 Ming Niu,2 Ai-Wu Wei,3 Jin-Fa Tang,3 Le Zhang,2 Jing Jing,2 Xiao-He Xiao,2 Jia-Bo Wang2,4 1Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2China Military Institute of Chinese Medicine, Fifth Me...

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Main Authors: Tu C, Niu M, Wei AW, Tang JF, Zhang L, Jing J, Xiao XH, Wang JB
Format: Article
Language:English
Published: Dove Medical Press 2021-03-01
Series:Journal of Inflammation Research
Subjects:
Online Access:https://www.dovepress.com/susceptibility-related-cytokine-panel-for-prediction-of-polygonum-mult-peer-reviewed-article-JIR
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author Tu C
Niu M
Wei AW
Tang JF
Zhang L
Jing J
Xiao XH
Wang JB
author_facet Tu C
Niu M
Wei AW
Tang JF
Zhang L
Jing J
Xiao XH
Wang JB
author_sort Tu C
collection DOAJ
description Can Tu,1,2 Ming Niu,2 Ai-Wu Wei,3 Jin-Fa Tang,3 Le Zhang,2 Jing Jing,2 Xiao-He Xiao,2 Jia-Bo Wang2,4 1Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2China Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China; 3The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, People’s Republic of China; 4School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, People’s Republic of ChinaCorrespondence: Jia-Bo WangSchool of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, People’s Republic of ChinaEmail pharm_sci@126.comXiao-He XiaoChina Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of ChinaEmail pharmacy302xxh@126.comBackground: Drug-induced liver injury is a common adverse effect in clinical practice, with severe cases resulting in liver failure and even death. Identification and prediction of individuals susceptible to idiosyncratic DILI continues to remain a challenge.Methods: In this study, we report that cytokines in human serum can be used to identify and predict individuals susceptible to Polygonum multiflorum-induced DILI (PM-DILI) in retrospective and prospective cohort studies.Findings: In the retrospective pilot study, we compared serum cytokine expression profiles of the PM-DILI group (n=10) and the PM-Tolerant group (n=12) and found 10 cytokines with significant differences. In the replication cohort study, differences in the 10 cytokines between PM-DILI (n =11) and PM-Tolerant (n=13) groups were verified. Among them, 6 cytokines showed no significant differences at two time points, including liver injury and recovery stage of PM-DILI, suggesting that these 6 cytokines have no correlation with PM-DILI, however, they may be related to susceptibility. Furthermore, all the retrospective cohorts were combined, and a PM-DILI susceptibility prediction model was built by screening the 6 cytokines. The combination of (TNF-α and CCL-2) or VEGF showed the highest sensitivity and specificity. Finally, the efficacy of the above 3 cytokine combination models in predicting PM-DILI-susceptible individuals was verified before PM exposure in another independent prospective cohort (n=24), with sensitivity and specificity of 66.7% and 83.3%, respectively.Conclusion: This proof-of-concept study demonstrates that the serum cytokine combination reflecting dysimmunity could be used as a new method to predict PM-DILI, thus providing a new perspective for improving the clinical management of IDILI.Keywords: drug-induced liver injury, Polygonum multiflorum, cytokine, prediction, susceptible individual
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spelling doaj.art-dd942942ec4545fcb4ed3919c8ac50482022-12-21T22:58:23ZengDove Medical PressJournal of Inflammation Research1178-70312021-03-01Volume 1464565562787Susceptibility-Related Cytokine Panel for Prediction of Polygonum multiflorum-Induced Hepatotoxicity in HumansTu CNiu MWei AWTang JFZhang LJing JXiao XHWang JBCan Tu,1,2 Ming Niu,2 Ai-Wu Wei,3 Jin-Fa Tang,3 Le Zhang,2 Jing Jing,2 Xiao-He Xiao,2 Jia-Bo Wang2,4 1Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2China Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China; 3The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, People’s Republic of China; 4School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, People’s Republic of ChinaCorrespondence: Jia-Bo WangSchool of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, People’s Republic of ChinaEmail pharm_sci@126.comXiao-He XiaoChina Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of ChinaEmail pharmacy302xxh@126.comBackground: Drug-induced liver injury is a common adverse effect in clinical practice, with severe cases resulting in liver failure and even death. Identification and prediction of individuals susceptible to idiosyncratic DILI continues to remain a challenge.Methods: In this study, we report that cytokines in human serum can be used to identify and predict individuals susceptible to Polygonum multiflorum-induced DILI (PM-DILI) in retrospective and prospective cohort studies.Findings: In the retrospective pilot study, we compared serum cytokine expression profiles of the PM-DILI group (n=10) and the PM-Tolerant group (n=12) and found 10 cytokines with significant differences. In the replication cohort study, differences in the 10 cytokines between PM-DILI (n =11) and PM-Tolerant (n=13) groups were verified. Among them, 6 cytokines showed no significant differences at two time points, including liver injury and recovery stage of PM-DILI, suggesting that these 6 cytokines have no correlation with PM-DILI, however, they may be related to susceptibility. Furthermore, all the retrospective cohorts were combined, and a PM-DILI susceptibility prediction model was built by screening the 6 cytokines. The combination of (TNF-α and CCL-2) or VEGF showed the highest sensitivity and specificity. Finally, the efficacy of the above 3 cytokine combination models in predicting PM-DILI-susceptible individuals was verified before PM exposure in another independent prospective cohort (n=24), with sensitivity and specificity of 66.7% and 83.3%, respectively.Conclusion: This proof-of-concept study demonstrates that the serum cytokine combination reflecting dysimmunity could be used as a new method to predict PM-DILI, thus providing a new perspective for improving the clinical management of IDILI.Keywords: drug-induced liver injury, Polygonum multiflorum, cytokine, prediction, susceptible individualhttps://www.dovepress.com/susceptibility-related-cytokine-panel-for-prediction-of-polygonum-mult-peer-reviewed-article-JIRdrug-induced liver injurypolygonum multiflorumcytokinepredictionsusceptible individual.
spellingShingle Tu C
Niu M
Wei AW
Tang JF
Zhang L
Jing J
Xiao XH
Wang JB
Susceptibility-Related Cytokine Panel for Prediction of Polygonum multiflorum-Induced Hepatotoxicity in Humans
Journal of Inflammation Research
drug-induced liver injury
polygonum multiflorum
cytokine
prediction
susceptible individual.
title Susceptibility-Related Cytokine Panel for Prediction of Polygonum multiflorum-Induced Hepatotoxicity in Humans
title_full Susceptibility-Related Cytokine Panel for Prediction of Polygonum multiflorum-Induced Hepatotoxicity in Humans
title_fullStr Susceptibility-Related Cytokine Panel for Prediction of Polygonum multiflorum-Induced Hepatotoxicity in Humans
title_full_unstemmed Susceptibility-Related Cytokine Panel for Prediction of Polygonum multiflorum-Induced Hepatotoxicity in Humans
title_short Susceptibility-Related Cytokine Panel for Prediction of Polygonum multiflorum-Induced Hepatotoxicity in Humans
title_sort susceptibility related cytokine panel for prediction of polygonum multiflorum induced hepatotoxicity in humans
topic drug-induced liver injury
polygonum multiflorum
cytokine
prediction
susceptible individual.
url https://www.dovepress.com/susceptibility-related-cytokine-panel-for-prediction-of-polygonum-mult-peer-reviewed-article-JIR
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