Study on the Immune Modulatory Activity of Seokjahaeki-tang Using Atopic Dermatitis Animal Models

아토피피부염 동물 병태 모델에서 석자해기탕(石紫解肌湯)의 면역조절작용에 관한 연구

  • Lee, Byung-Woong (Department of Pathology, College of Oriental Medicine, Daejeon University) ;
  • Gim, Seon-Bin (Traditional and Biomedical Research Center(TBRC), Daejeon University) ;
  • Song, Hyang-Hee (Department of Health Skincare, Byuksung College) ;
  • Ji, Joong-Gu (Department of Oriental Health Care, Joongbu University) ;
  • Bak, Ji-Won (Traditional and Biomedical Research Center(TBRC), Daejeon University) ;
  • Kim, Dong-Hee (Department of Pathology, College of Oriental Medicine, Daejeon University)
  • 이병웅 (대전대학교 한의과대학 병리학교실) ;
  • 김선빈 (대전대학교 난치성면역질환의동서생명의학연구센터) ;
  • 송향희 (벽성대학 헬스스킨케어과) ;
  • 지중구 (중부대학교 한방건강관리학과) ;
  • 박지원 (대전대학교 난치성면역질환의동서생명의학연구센터) ;
  • 김동희 (대전대학교 한의과대학 병리학교실)
  • Received : 2012.07.10
  • Accepted : 2012.08.20
  • Published : 2012.08.25

Abstract

In order to evaluate the efficacy of SHT against atopic dermatitis (AD), various immune related cytokines as well as histological comparison were performed in animal models, and the results are described. Clinical skin index of the SHT treated group decreased significantly in weeks 11 and 13, compared to the control group. Also, CD4+ immune cell ratio in the dorsal skin was significantly decreased to 69%, and both epidermal and dermal skin thickness was decreased. Serum IL-4, IL-5, IL-6, IL-13, and TNF-${\alpha}$, which are all important markers of inflammation, were decreased to 64%, 44%, 87%, 48%, and 45%, respectively. The expression of histamine, a chemical transmitter increasingly released during the progression of inflammation, was significantly decreased to 47%. The production of IgE immunoglobulin was significantly decreased to 16% compared to the control group. In conclusion, SHT pacifies the activation of T cells, leading to suppression of both Th2 cytokine overexpression and infiltration of immune cells into skin. As a result, relative thinning of both epidermis and dermis were observed. With the results obtained from in vitro studies, the immune modulatory effect of SHT in AD animal models was experimentally demonstrated. This study should provide solid information to construct EBM and for clinical practice.

Keywords

References

  1. Holden, C.A. and Parish, W.E. Atopic dermatitis. Blackwell Science, Oxford, 1998.
  2. Kang mo Ahn, Role of mast cells in allergic inflammation and innate immunity. Korean Journal of Pediatrics 47(11):1137-1141, 2004.
  3. Shea, K.M., Truckner, R.T., Weber, R.W., Peden, D.B. Climate change and allergic disease. J Allergy Clin Immunol 122: 443-453, 2008. https://doi.org/10.1016/j.jaci.2008.06.032
  4. Epstein, P.R. Climate change and human health. N Engl J Med 353: 1433-1436, 2005. https://doi.org/10.1056/NEJMp058079
  5. Galli, S.J., Gordon, J.R., Wershil, B.K. Mast cell cytokines in allergy and inflammation. Agents Actions Suppl, 43: 209-201, 1993.
  6. Agnello, D., Lankford, C.S., Bream, J., Morinobu, A., Gadina, M., O'shea, J.J. and Frucht, D.M. Cytokines and transcription factors that regulate T helper cell differentiation: new players and new insights. J Clin Immunol 23: 147-161, 2003. https://doi.org/10.1023/A:1023381027062
  7. Metcalfe, D.D., Baram, D., Mekori, Y.A. Mast cells, Physiol Rev. 77: 1033-1079, 1997.
  8. Leung, D.Y.M. Pathogenesis of atopic dermatitis. J Allergy Clin Immunol 104: S99-108, 1999. https://doi.org/10.1016/S0091-6749(99)70051-5
  9. Kevin, D.C. Atopic dermatitis: recent trends in pathogenesis and therapy. J invest Dermatol 102: 128-137, 1994. https://doi.org/10.1111/1523-1747.ep12371746
  10. Leung, D.Y. Atopy dermatitis: new insight and apportunities for for therapeutic intervention, J Allergy Clin Immunol 105: 860-867, 2000. https://doi.org/10.1067/mai.2000.106484
  11. N. Novak, D. Simon, Atopic dermatitis - from new pathophysiologic insights to individualized therapy. Allergy 66(7):830-839, 2011. https://doi.org/10.1111/j.1398-9995.2011.02571.x
  12. Andreas Wollenberg, Christina Schnopp, Evolution of Conventional Therapy in Atopic Dermatitis. Immunology and Allergy Clinics of North America 30(3):351-368, 2010. https://doi.org/10.1016/j.iac.2010.06.005
  13. 王保方외. 皮膚病中醫診療學, 인민위생출판사, pp 254-255, 310-311, 351-354, 2000.
  14. 馬紹堯. 實用中醫皮膚病學, 상해중의약대학출판사, pp 244-246, 1999.
  15. 장서현 외. 皮膚科券, 학원출판사, pp 299-230, 2004.
  16. 박선민. 피부세포에서 아토피 피부염의 유발과 관련된 PAR-2 및 사이토카인의 발현을 감소시키는 한약재 탐색, 동의생리병리학회지 25(2):270-274, 2011.
  17. 고홍윤 외. 아토피 피부염에 대한 고삼가미방과 청기패독산의 겸용 투여 효과, 동의생리병리학회지 23(6):1281-1291, 2009.
  18. 김혜림. 淸肌消毒湯이 아토피피부염 염증 관련 인자에 미치는 영향, 대전대학교 한의학연구소 논문집, 20(2):41-52, 2012.
  19. 排毒丸의 아토피피부염 병태모델에서의 면역 억제 효능, 동의생리병리학회지 24(5):796-806, 2010.
  20. 정대웅 외. 석자해기탕이 아토피 피부염 유관인자인 산화적 손상과 염증 인자에 미치는 영향, 대전대학교 한의학연구소 논문집, 20(2):53-65, 2012.
  21. Blaser Kurt, Ring Johannes and Capron, T Cell Regulation in Allergy, Asthma and Atopic Skin Diseases. S Karger Pub, pp 121-137, 2008.
  22. 박영립, 박 준, 아토피 피부염의 병인, 대한피부연구학회지 14(3):67-72, 2007.
  23. Beellanti, J.A., Cytokine and allergic disease; clinical aspect. Allergy Asthma Proc 19(6):337-341, 1998. https://doi.org/10.2500/108854198778612735
  24. 조수익, 김진혜, 정보영, 안인수, 김혜원, 박천욱, 이철헌. 소아청소년 아토피피부염 환자의 삶의 질. 대한피부과학회지 49(5):415-421, 2011.
  25. Wollenberg, A., Kraft, S., Oppel, T., Bieber, T. Atopic dermatitis: pathogenetic mechanism. Clin Exp Dermatol 25: 530-534, 2000. https://doi.org/10.1046/j.1365-2230.2000.00699.x
  26. Schmid-Grendelmeier, P., Altznauer, F., Fischer, B., Bizer, C., Straumann, A., Menz, G., et al., Eosinophils express functional IL-13 in eosinophilic inflammatory disease. J Immunol. 169: 1021-1027, 2002.
  27. Zhu, Z., et al., Pulmonary expression of interluekin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities and eotaxin production. J Clin Invest, 103: 779-788, 1999. https://doi.org/10.1172/JCI5909
  28. Wills-Karp, M., Chiaramonte, M. Interleukin-13 in Asthma. Curr Opin Pulm Med. 9(1):21-7, 2003. Review. https://doi.org/10.1097/00063198-200301000-00004
  29. Church, M.K., Bradding, P., Walls, A.F., Okayama, Y. Human mast cells and basophils. In Allergy and allergic diseases. 1st ed. MA : Blackwell Science pp 149-170, 1997.
  30. Gauchat, J.F., et al., Induction of human IgE synthesisin B cells by mast cells and basophils. Nature 365: 340-343, 1993. https://doi.org/10.1038/365340a0
  31. A. Svensson, C. Chambers, A. Ganemo, S.A. Mitchell, A systematic review of tacrolimus ointment compared with corticosteroids in the treatment of atopic dermatitis. Current Medical Research and Opinion 27(7):1395-1406, 2011. https://doi.org/10.1185/03007995.2011.582483
  32. Eric L. Simpson, Atopic dermatitis: a review of topical treatment options. Current Medical Research and Opinion 26(3):633-640, 2010. https://doi.org/10.1185/03007990903512156
  33. 荊芥連翹湯과 加味荊芥連翹湯이 消炎.鎭痛및 抗알레르기에 미치는 影響, 원광대학교대학원, 1997.
  34. 김민지. 형개연교탕의 물추출물이 lipopolysaccharide로 유도된 Raw264.7cell에서의 Nitric Oxide의 생성 및 iNOS와 COX-2의 발현, Cytokine에 미치는 영향, 대구한의대학교대학원, 2005.
  35. 유태섭. 荊芥連翹湯의 항알레르기작용에 대한 실험적 효과, 대한한방 소아과학회지 4(1):19-30, 1990.
  36. 姜蘭伊. 아토피피부염 동물 병태 모델에서의 형개연교탕의 면역조절작용, 대전대학교대학원, 2010.
  37. 金德坤. 紫草가 아토피 피부염에 미치는 영향, 慶熙大學校大 學院, 2004.
  38. 鄭明我. 아토피성 피부염 유발 NC/Nga mice 동물 모델에 있어 삼백초, 어성초, 자초로 구성된 복합처방의 항아토피 작용, 木浦大學校大學院, 2010.
  39. Vestergard, C., et al The Nc/Nga mouse: a model for atopic dermatitis. Mol Med Today 5: 209-210, 2000.
  40. Romagnani, S. immunologic influences on allergy and the Th1/Th2 balance. J Allergy Clin Immunol 113: 395-400, 2004. https://doi.org/10.1016/j.jaci.2003.11.025
  41. Matsuda, H., et al., Development of atopic dermatitis-like skin lesion with IgE hyperproduction in Nc/Nga mice. Int. Immunol 9: 461-466, 1997. https://doi.org/10.1093/intimm/9.3.461
  42. Everett H. Meyer, Rosemarie H. DeKruyff, and Dale T. Umetsu, T Cells and NKT Cells in the Pathogenesis of Asthma, Annual Review of Medicine 59: 281-292, 2007.
  43. Helena Aniansson Zdolsek, Jan Ernerudh, Patrick G. Holt, Joacim Nilsson, Bengt Bjorksten, Expression of the T-Cell Markers CD3, CD4 and CD8 in Healthy and Atopic Children during the First 18 Months of Life. Arch Allergy Immunol 119: 6-12, 1999. https://doi.org/10.1159/000024169
  44. D.B. Peden, Development of atopy and asthma: candidate environmental influences and important periods of exposure. Environ Health Perspect. 108(Suppl 3):475-482, 2000.
  45. Toshiaki Kawakami, Stephen J. Galli, Regulation of mast-cell and basophil function and survival by IgE. Nature Reviews Immunology 2: 773-786, 2002. https://doi.org/10.1038/nri914