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Wednesday, August 17th, 2022

 

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Title:
Expression of NF-κB/IL-6 Pathway in Postherpetic Neuralgia Regulates Th17/Treg Immune Balance
Authors:  Haiou Zhou, B.S., Binghui Wang, M.M., Jingjing Gao, B.S., Zhoujia Tao, B.S., and Long Lei, B.S.
  Objective: To study the role and significance of Th17/Treg immune balance in the pathogenesis of postherpetic neuralgia (PHN), and to explore the effect of NF-κB/IL-6 pathway on the peripheral blood Th17/Treg immune balance of patients with PHN.
Study Design:
The percentages of Treg cells and Th17 cells in peripheral blood mononuclear cells (PBMCs) of 40 healthy controls and 40 patients with PHN were detected by flow cytometry (FCM). Immunocytochemistry was used to detect NF-κB positive cell percentage difference between the peripheral blood of healthy controls and patients with PHN. ELISA and RT-PCR measured the transcription and expression of TGF-β and IL-6 in peripheral blood of healthy controls and patients with PHN. FCM was utilized to detect the percentages of Treg cells and Th17 cells in PBMCs and the ratio between Treg cells and Th17 after blocking the NF-κB/IL-6 signaling pathway with NF-κB inhibitor PDTC and IL-6 inhibitor Actemra.
Results:
According to FCM identification, the percentage of Treg cells in the peripheral blood of patients with post–herpes zoster neuralgia was significantly lower than that of the healthy control group (p<0.05). The percentage of Th17 cells was significantly higher than that of the healthy control group (p<0.05). Treg/Th17 cell ratio was considerably lower than that of the healthy control group (p<0.01). Immunocytochemistry experiments showed that the percentage of NF-κB positive cells in the peripheral blood cells of patients with PHN was significantly higher than that of the healthy control group (p<0.01). The expression and transcription levels of TGF-β and IL-6 in the peripheral blood of patients with PHN were significantly increased (p< 0.01). Compared with the control group without the inhibitor, applying inhibitors such as PDTC and Actemra can substantially increase the ratio of Treg/Th17 cells in the peripheral blood of the PHN patient group (p< 0.05). CCK8 experiments showed that NF-κB inhibitor PDTC and IL-6 inhibitor Actemra could promote cell proliferation in PHN patients.
Conclusion:
The NF-κB/IL-6 pathway in the peripheral blood of patients with PHN is activated, which makes the differentiation of Treg/Th17 unbalanced. Related inhibitors of this pathway can inhibit the differentiation of Th17 and induce the generation of Treg cells. The imbalance of Treg/Th17 was restored to a certain extent.
Keywords:  herpes zoster, IL-6 pathway, NF-κB, postherpetic neuralgia, shingles, Th17 cells, transcription factor, Treg cells
   
   
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