Susceptibility-Related Cytokine Panel for Prediction of Polygonum multiflorum-Induced Hepatotoxicity in Humans
Authors Tu C, Niu M, Wei AW, Tang JF, Zhang L, Jing J, Xiao XH, Wang JB
Received 5 January 2021
Accepted for publication 13 February 2021
Published 4 March 2021 Volume 2021:14 Pages 645—655
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Professor Ning Quan
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 China
Correspondence: Jia-Bo Wang
School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, People’s Republic of China
Email [email protected]
China Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China
Email [email protected]
Background: 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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