DOI QR코드

DOI QR Code

Effect of Korean Red Ginseng on Serum Soluble CD8 in HIV-1-Infected Patients

고려홍삼이 HIV-1 감염자에서 혈청 soluble CD8 항원 농도에 미치는 영향

  • Cho, Young-Keol (Department of Microbiology, University of Ulsan College of Medicine) ;
  • Sung, Heung-Sup (Department of Microbiology, University of Ulsan College of Medicine)
  • 조영걸 (울산대학교 의과대학 미생물학교실) ;
  • 성흥섭 (울산대학교 의과대학 미생물학교실)
  • Published : 2007.12.31

Abstract

To evaluate whether there is a relation between Korean red ginseng (KRG)-intake and the suppression of immune hyperactivation in HIV-1-infected patients, we measured serum soluble CD8 (sCD8) over 31-48 months in 168 patients. They were divided into four groups; HIV-1-infected control (n = 49), zidovudine (ZDV) group (n = 22), KRG group (n = 48), and combination of KRG and ZDV group (n = 49). In control, sCD8 and the ratio of sCD8/CD8+ T cells significantly increased by 33% (paired t-test, P < 0.05) and 54% over $21\;{\pm}\;13$ months (P < 0.001), respectively. In ZDV group, sCD8 decreased within first 6 months and then showed steady increase and the ratio also increased over $19\;{\pm}\;10$ months. In KRG group, sCD8 and the ratio of sCD/CD8+ T cells continuously decreased by 45% (P < 0.01) and 19% over $19\;{\pm}\;11$ months (P < 0.05), respectively. In combination group, sCD8 gradually decreased by 29% (P < 0.01). There was a clear difference in the changes in serum sCD8 over time among 4 groups. There was no rebound phenomenon in KRG group as shown in ZDV group. These results suggest that KRG-intake suppresses immune hyperactivation state by HIV antigen itself in the HIV-infected patients.

고려홍삼이 HIV-1 감염자에게서 바이러스의 활발한 증식으로 유발된 면역계의 과활성화를 장기간에 걸쳐 억제하는지 살펴보기 위해 면역 활성화 지표인 soluble CD8항원(sCD8)을 측정하였다. HIV-1 감염 대조군 49명, zidovudine (ZDV) 복용군 22명, KRG 복용군 48명, KRG와 ZDV 병용군(49명)을 대상으로 하였다. HIV-1 감염 대조군에서는 혈청 sCD8 농도가 31-48개월 동안 33% 증가하였으며(P < 0.05), sCD8/CD8+T 림프구 비도 $21{\pm}13$개월동안 54% 증가하였다(P < 0.001). ZDV 복용군에서는 혈청 sCD8농도가 초기 6개월 동안은 감소하였으나 그 이후로는 서서히 증가하였으며, sCD8/CD8+T 림프구 비도 증가하였다. KRG 복용군은 sCD8 농도가 31-48개월 동안 45% 감소하였으며(P < 0.01), sCD8/CD8+T 림프구 비도 $19\;{\pm}\;11$개월 동안 19% 감소하였다(P < 0.05). 병용군에서는 sCD8 농도가 31-48개월 동안 29%(P < 0.01) 감소하였다. 추적관찰 기간 동안 각 군간의 sCD8 농도 변화가 명확한 차이를 보였으며, KRG 복용군에서는 ZDV 복용군에서 관찰된 'rebound현상'(sCD8이 초기에 감소하다가 다시 증가하는 경향)이 없었다. 결론적으로 본 연구에서는 HIV-1 감염환자에서 KRG를 장기간 복용시켰을 경우 sCD8 농도가 지속적으로 감소하여, KRG가 면역계의 소모적인 과활성화 상태를 방지함을 알 수 있었다.

Keywords

References

  1. Panel on Clinical Practices for Treatment of HIV Infection: Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. http://aidsinfo.nih.gov/ guidelines/ (2004)
  2. Boucher, C. A., O'Sullivan, E., Mulder, J. W., Ramautarsing, C., Kellam, P., Darby, G., Lange, J. M., Goudsmit, J., and Larder, B. A.: Ordered appearance of zidovudine resistance mutations during treatment of 18 human immunodeficiency virus-positive subjects. J. Infect. Dis. 165, 105-110 (1992) https://doi.org/10.1093/infdis/165.1.105
  3. Reddy, M. M., McKinley, G., Englard, A., and Grieco, M. H.: Effect of azidothymidine (AZT) on HIV P24 antigen, beta 2- microglobulin, neopterin, soluble CD8, soluble interleukin-2 receptor and tumor necrosis factor alpha levels in patients with AIDS-related complex or AIDS. Int. J. Immunopharmacol. 12, 737-741 (1990) https://doi.org/10.1016/0192-0561(90)90036-M
  4. Siller, L., Martin, N. L., Kostuchenko, P., Beckett, L., Rautonen. J., Cheng, S. C., and Wara, D.W.: Serum levels of soluble CD8, neopterin, beta 2-microglobulin and p24 antigen as indicators of disease progression in children with AIDS on zidovudine therapy. AIDS 7, 369-373 (1993)
  5. Nishanian, P., Hofmann, B., Wang, Y., Jackson, A. L., Detels, R., and Fahey, J. L.: Serum soluble CD8 molecule is a marker of CD8 T-cell activation in HIV-disease. AIDS 5, 805–812 (1991)
  6. Tomkinson, B. E., Brown, M. C., Ip, S. H., Carrabis, S., and Sullivan, J.L.: Soluble CD8 during T cell activation. J. Immunol. 142, 2230-2236 (1989)
  7. Sewell, A. K., Gerth U. C., Price D. A., Purbhoo M. A., Boulter J. M., Gao G. F., Bell J. I., Phillips R. E., and Jakobsen B. K.: Antagonism of cytotoxic T-lymphocyte activation by soluble CD8. Nat. Med. 5, 399-404 (1999) https://doi.org/10.1038/7398
  8. Kahn, J.O. and Walker, B.D.: Acute human immunodeficiency virus type 1 infection. N. Engl. J. Med. 339, 33-39 (1998) https://doi.org/10.1056/NEJM199807023390107
  9. Cho Y. K, Kim Y. K, Lee, I., Choi, M. H., and Shin, Y. O.: The effect of Korean red ginseng(KRG), zidovudine, and the combination of KRG and ZDV on HIV-infected individuals. J Korean Soc. Microbiol. 31, 353-360 (1996)
  10. Cho, Y. K., Kim Y. B., Choi, B. S., Kim, Y. K., Choi, M. H., Jang, Y. S., and Shin, Y. O.: Effect of Korean red ginseng on the levels of serum p24 antigen, $beta_2$ -microglobulin and CD4+ T cell counts in HIV (I). J. Korean Society Microbiol. 28, 409-417 (1993).
  11. Cho, Y. K., Kim, Y. B., Choi, B. S., Cho, Y. J., Suh, I. S., and Shin, Y. H.: The increase of T cell by Korean red ginseng in HIV-infected individuals. J. Korean Society Microbiol. 29, 371-379 (1994)
  12. Cho, Y. K., Kim, Y. B., Kim, Y. K., Lee, H. J., and Oh, W. I.: Sequence analysis of C2-V3 region of human immunodeficiency virus type 1 gp120 and its correlation with clinical significance: the effect of long-term intake of Korean red ginseng on env gene variation. J. Korean Soc. Microbiol. 32, 611-623 (1997)
  13. Cho, Y. K., Lee, W. S., Cheng, K. S., Kim, S. S., and Shin, Y. O.: The levels of CD4 antigen and soluble CD8 in the asymptomatic HIV-infected sera. J. Korean Society Microbiol. 26, 367-373 (1991)
  14. Yagi, M. J., Chu, F. N., Jiang, J. D., Wallace, J., Mason, P., Liu, Y., Carafa, J., and Bekesi, J. G.: Increases in soluble CD8 antigen in plasma, and CD8+ and CD8+CD38+ cells in human immunodeficiency virus type-1 infection. Clin. Immunol. Immunopathol. 63, 126-134 (1992) https://doi.org/10.1016/0090-1229(92)90004-8
  15. Cho, Y. K., Lee, H. J., Sung, H., Kim, Y. K., Kim, Y. B., Lee, Y., Kim, M. J., Kim, D. G., Won, Y. H., and Cho, G. J.: Detection of mutations to zidovudine in the pol gene of human immunodeficiency virus-a by direct sequencing. J. Korean Soc. Virology 29, 271-281 (1999)
  16. Cho, Y. K., Sung, H., Ahn, S. H., Bae, I. G., Woo, J. H., Won, Y. H., Kim, D. G., and Kang, M. W.: Frequency of mutations conferring resistance to nucleoside reverse transcriptase inhibitors in human immunodeficiency virus type 1-infected patients in Korea. J. Clin. Microbiol. 40, 1319-1325 (2002) https://doi.org/10.1128/JCM.40.4.1319-1325.2002
  17. Sung, H., Kang, S. M., Lee, M. S., Kim, T. G., and Cho, Y. K.: Korean red ginseng slows depletion of CD4 T cells in human immunodeficiency virus type 1-infected patients. Clin. Diagn. Lab. Immunol. 12, 497-501 (2005)
  18. Cho, Y. K., Sung, H., Kim, T. K., Lim, J., Jung, Y. S., and Kang, S. M.: Korean red ginseng significantly slows CD4 T cell depletion over 10 years in HIV-1 infected patients: association with HLA. J. Ginseng Res. 28, (2004)
  19. Cho, Y. K., Sung, H., Lee, H. J., Joo, C. H., and Cho, G. J.: Long-term intake of Korean red ginseng in HIV-1-infected patients: development of resistance mutation to zidovudine is delayed. Int. Immunopharmacol. 1, 1295-1305 (2001) https://doi.org/10.1016/S1567-5769(01)00061-3
  20. Andrieu, J. M., Lu, W., and Levy, R.: Sustained increases in CD4 cell counts in asymptomatic human immunodeficiency virus type 1-seropositive patients treated with prednisolone for 1 year. J. Infect. Dis. 171, 523-530 (1995) https://doi.org/10.1093/infdis/171.3.523
  21. Nocerino, E., Amato, M., and Izzo, A. A.: The aphrodisiac and adaptogenic properties of ginseng. Fitoterapia 71 Suppl 1, S1-S5 (2000)
  22. Ng, T. B. and Wang, H.: Panaxagin, a new protein from Chinese ginseng possesses anti-fungal, anti-viral, translationinhibiting and ribonuclease activities. Life Sci. 68, 739-749 (2001) https://doi.org/10.1016/S0024-3205(00)00970-X
  23. Wang, H. X. and Ng, T. B.: Quinqueginsin, a novel protein with anti-human immunodeficiency virus, antifungal, ribonuclease and cell-free translation-inhibitory activities from American ginseng roots. Biochem. Biophys. Res. Commun. 269, 203-208 (2000) https://doi.org/10.1006/bbrc.2000.2114
  24. Schindler, M., Munch, J., Kutsch, O., Li, H., Santiago, M. L., Bibollet-Ruche, F., Muller-Trutwin, M. C., Novembre, F. J., Peeters, M., Courgnaud, V., Bailes, E., Roques, P., Sodora, D. L., Silvestri, G., Sharp, P. M., Hahn, B. H. and Kirchhoff, F.: Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1. Cell. 125, 1055- 67 (2006) https://doi.org/10.1016/j.cell.2006.04.033

Cited by

  1. Enhancement of low molecular weight ginsenosides from low-quality ginseng through ultra-high-pressure and fermentation processes vol.237, pp.3, 2013, https://doi.org/10.1007/s00217-013-2007-9