Research Articles

Wenshen Jianpi recipe (温肾健脾方) induced immune reconstruction and redistribution of natural killer cell subsets in immunological non-responders of human immunodeficiency virus/acquired immune deficiency syndrome: a randomized controlled trial

  • Zhuang TAO ,
  • Jian WANG ,
  • Xin CHEN ,
  • Yonghong LI ,
  • Yuguang YAN ,
  • Ao ZHANG ,
  • Wen ZOU ,
  • Ying LIU
Expand
  • 1 Research Center of AIDS Treatment with Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China; Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China
    2 Research Center of AIDS Treatment with Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China
    3 Department of Integrated Traditional Chinese and Wetern Medicine, Kunming Hospital of Traditional Chinese Medicine, Kunming 650000, China
    4 Department of Infection, No.6 People's Hospital of Shenyang City, Shenyang 110006, China
    5 University of Chinese Academy of SoCIal SCIences, Beijing, 100102, China
LIU Ying, Research Center of AIDS Treatment with Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China. liuying0516@163.com Telephone: +86-13552252730; +86-13021985109
ZOU Wen, Research Center of AIDS Treatment with Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China. veven@yeah.net;

Received date: 2021-05-11

  Accepted date: 2021-08-20

  Online published: 2022-05-19

Supported by

National Science and Technology Major Project of China During the 13th Five-year Plan Period: New Adjuvant Strategies of Traditional Chinese Medicine on Immune Reconstruction for Long-term ART-treated People Living with HIV(2017ZX10205501);Effects of Traditional Chinese Medicine on Intestinal Bacterial Community Structure of AIDS Patients(2017ZX10205501-001-010);National Natural Science Foundation of China: Immune Mechanism of Immunological Non-responders of HIV/AIDS Treated with Traditional Chinese Medicine from Immune Activation and Toll like Receptor Signal Pathway(81503571)

Abstract

OBJECTIVE: To evaluate the effects of the Wenshen Jianpi recipe (温肾健脾方, WJR) on immune reconstruction and natural killer (NK) cells in immunological non-responders (INRs) of people living with human immunodeficiency virus (HIV) (PLWH) and propose new therapeutic strategies for HIV.

METHODS: Based on Traditional Chinese Medicine treatment principle “invigorating Qi and warming Yang in the spleen and kidneys”, WJR combined with antire-troviral therapy (ART) therapy was performed in a randomized, double-blind, placebo-controlled study of 60 patients with non-responders. The randomized process was executed by the Clinical Evaluation Center of China Academy of Chinese Medical Sciences. Sixty patients who met the inclusion criteria obtained random numbers (that is the drug number) was randomly divided into a treatment group and a placebo control group according to a 1∶1 ratio. CD4+T cell counts and natural killer (NK) cells counts were evaluated at baseline and 12-week, 24-week follow-ups.

RESULTS: Four participants received random numbers and did not enter the group due to the patient's own reasons. A total of 56 patients were enrolled, including 28 in the treatment group and 28 in the control group. CD4+T cell counts in the treatment group were significantly increased at week 24 (P = 0.01 < 0.05), which were significantly higher than those in the control group (P = 0.01 < 0.05). Although no significant differences were observed between two groups, the CD56briCD16- NK cell counts in the treatment group were significantly increased after duration. and CD56dimCD16+ NK cell counts in the treatment group were significantly higher than those in the control group after 24 weeks of treatment (P = 0.025 < 0.05). As compared with the control group, the treatment group had significantly lower CD56negCD16+ NK cell counts after 24 weeks of treatment (P = 0.023 < 0.05).

CONCLUSIONS: WJR promotes the immune reconstruction of INRs and redistribution of NK cell subsets, notably decreasing CD56negCD16+ NK cell counts in INRs. However, the redistribution of NK cell subsets is not beneficial for immune reconstruction in INRs. Further large-scale RCTs are required to evaluate the effect of WJR on immune recovery in INRs and decipher the underlying mechanism.

Cite this article

Zhuang TAO , Jian WANG , Xin CHEN , Yonghong LI , Yuguang YAN , Ao ZHANG , Wen ZOU , Ying LIU . Wenshen Jianpi recipe (温肾健脾方) induced immune reconstruction and redistribution of natural killer cell subsets in immunological non-responders of human immunodeficiency virus/acquired immune deficiency syndrome: a randomized controlled trial[J]. Journal of Traditional Chinese Medicine, 2022 , 42(5) : 795 -802 . DOI: 10.19852/j.cnki.jtcm.20220519.005

References

1. Lizdany F-Á, Juan CH, Wildeman Z. NK cells in HIV-1 infection: from basic science to vaccine strategies. Front Immunol 2018; 9: 1-10.
2. Anthony SF, Clifford LH. Four decades of HIV/AIDS - much accomplished, much to do. New Engl J Med 2020; 383: 1-4.
3. Quillay H, Costa HE, Duriez M, et al. NK cells control HIV-1 infection of macrophages through soluble factors and cellular contacts in the human decidua. Retrovirology 2016; 13: 1-11.
4. Marcus A, Lena F, Davor F, Nina B. DCs and NK cells: critical effectors in the immune response to HIV-1. Nat reviews Immunol 2011; 11: 176.
5. Jiang YJ, Yang M, Sun XJ, et al. IL-10+ NK and TGF-β+NK cells play negative regulatory roles in HIV infection. BMC Infect Dis 2018; 18: 80.
6. Wang YT, Lawrence L, Kyle G, et al. HIV-1-induced cytokines deplete homeostatic innate lymphoid cells and expand TCF7-dependent memory NK cells. Nat Immuno 2020; 21: 1-13.
7. Liu ZB, Yang JP, Xu LR. Effectiveness and safety of Traditional Chinese Medicine in treating acquired immune deficiency syndrome: 2004-2014. Infect Dis Poverty 2015; 4: 59.
8. Tao Z, Huang XJ, Liu Y, et al. Efficacy of integrated Traditional Chinese Medicine and anti-retroviral therapy on immunological nonresponse in patients with human immunodeficiency virus/acquired immunodeficiency syndrome: a Meta-analysis of randomized controlled trials. J Tradit Chin Med 2021; 41: 669-676.
9. Esposito F, Carli I, Vecchio CD, et al. Sennoside A, derived from the Traditional Chinese Medicine plant Rheum L., is a new dual HIV-1 inhibitor effective on HIV-1 replication. PhytoMedicine 2016; 23: 1383-91.
10. Xu LJ, Nicole G, Claudia DV, et al. From the Traditional Chinese Medicine plant Schisandra chinensis new scaffolds effective on HIV-1 reverse transcriptase resistant to non-nucleoside inhibitors. J microbio (Seoul, Korea) 2015; 53: 288-93.
11. Li TS, Xie J, Li YJ, et al. Tripterygium wilfordii Hook F extract in cART-treated HIV patients with poor immune response: a pilot study to assess its immunomodulatory effects and safety. HIV Clin Trials 2015; 16: 49-56.
12. Sun WX, Liu Y, Zhou W, Li HW, Yang J, Chen ZB. Shikonin inhibits TNF-α production through suppressing PKC-NF-κB-dependent decrease of IL-10 in rheumatoid arthritis-like cell model. J Nat Med-Tokyo 2017; 71: 349-56.
13. Liu Y, Wang J, Zou W, et al. Effect of immune No. 2 granule on CD4+ T counts of AIDS patients with immune reconstitution deficiency after HAART. Zhong Yi Za Zhi 2017; 58: 34-7.
14. Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. Int J Surg 2011; 9: 672-7.
15. Giovanna QM, Alfonso N, Massimo S, LuCIana G, Benedetta M, Marina V. HIV-1 Nef impairs the dynamic of DC/NK crosstalk: different outcome of CD56 (dim) and CD56 (bright) NK cell subsets. FASEB J 2007; 21: 2323.
16. Carolyn R, A DK, P KE, et al. Generation of cellular immune memory and B-cell immunity is impaired by natural killer cells. Nat Commun 2015; 6: 1-14.
17. Wang J, Liu Y, He LY, et al. Distribution and development rules of Chinese Medicine syndromes in 2237 cases of HIV/AIDS. Zhong Yi Za Zhi 2012; 53: 948-51.
18. Wang W. Syndromes of the patients with HIV/AIDS before and after ART treatment and incomplete immune reconstruction. Beijing: China Academy of Medical SCIences, 2015: 67-74.
19. Li HJ, Guo HJ, Liu Y, et al. Thermal state data and clinical significance of cold or heat syndromes in HIV/AIDS patients. Beijing Zhong Yi Yao Da Xue Xue Bao (Zhong Yi Lin Chuang Ban) 2011; 18: 43-5.
20. Hou L, Li HJ, Wang J. Initial exploration of infrared imaging characteristics in HIV-infected patients. Shi Jie Zhong Xi Yi Jie He Za Zhi 2011; 6: 487-90.
21. Zou W, Wang J, Gao GJ, et al. Effects of TLR4 and TLR9 in immunological unresponsiveness AIDS patients treated with Yiqi Jianpi Granules combined with HAART. Zhong Hua Zhong Yi Yao Za Zhi 2019; 34: 4426-28.
22. Zou W, Wang J, Liu Y, Yang QL, Gao GJ, Zhang FC. Effects of Traditional Chinese Medicine combined with HAART therapy on the level of toll like receptors m RNA in AIDS patients with incomplete immune reconstitution. Zhong Hua Zhong Yi Yao Za Zhi 2017; 32: 5672-74.
23. Milush JM, López-Vergès S, York VA, Deeks SG, Nixon DF. CD56negCD16+ NK cells are activated mature NK cells with impaired effector function during HIV-1 infection. Retrovirology 2013; 10: 158.
24. Gregor FL, Cheng WJ, Yagmur F, et al. Virologically suppressed HIV patients show activation of NK cells and persistent innate immune activation. J Immuno 2012; 189: 1491-99.
25. LetiCIa, Kuri-Cervantes, Salgado-Montes G, et al. Activation of NK cells is associated with HIV-1 disease progression. J Leukocyte Biol 2014; 96: 7-16.
26. Luo ZW, Li Z, Lisa M, et al. Increased natural killer cell activation in HIV-infected immunologic non-responders correlates with CD4+ T cell recovery after antiretroviral therapy and viral suppression. PLoS One 2017; 12: e0167640.
27. Ilan A, Mahlab GK, Daniel E, et al. Characteristics and outcome of patients diagnosed With HIV at older age. Medicine 2016; 95: e2327.
28. Mitchai M, Leeratanapetch N, Lulitanon DV, et al. Phenotypic characteristics and function of NK cell subsets in cART-treated HIV-1-infected individuals. World J AIDS 2014; 4: 293-300.
29. Raquel T, Javier GC, Olga D, et al. Selective depletion of CD56(dim) NK cell subsets and maintenance of CD56 (bright) NK cells in treatment-naive HIV-1-seropositive individuals. J Clin Immun 2002; 22: 176-83.
30. Xu J, Zhang J, Wang J. The application of Traditional Chinese Medicine against the tumor immune escape. J Transl Intern Med 2020; 8: 203-4.
31. Lan TJ, Luo XF, Mo MY, et al. Hydrolyzed seawater pearl tablet modulates the immunity via attenuating Th1/Th2 imbalance in an immunosuppressed mouse model. J Tradit Chin Med 2021; 41: 397-405.
32. Zhou ZJ, Liu XH, Wu TT, et al. Herbal formula of Bushen Jianpi (补肾健脾方) combined with sorafenib inhibits hepatocellular carCInoma growth by promoting cell apoptosis and blocking the cell cycle. J Tradit Chin Med 2021; 41: 194-202.
Outlines

/