Ann Dermatol.  2014 Apr;26(2):221-230. 10.5021/ad.2014.26.2.221.

Immunomodulatory Effects of Balneotherapy with Hae-Un-Dae Thermal Water on Imiquimod-Induced Psoriasis-Like Murine Model

Affiliations
  • 1Department of Dermatology, School of Medicine, The Catholic University of Korea, Seoul, Korea. jwkim52@catholic.ac.kr
  • 2Department of Microbiology, Ewha Womans University School of Medicine, Seoul, Korea. soyounwoo@ewha.ac.kr
  • 3Department of Earth and Environmental Sciences, Korea University, Seoul, Korea.
  • 4The Korea Central Institute of Hot Springs, Seoul, Korea.
  • 5Oh&Kim's Aesthetic Clinic, Seoul, Korea.

Abstract

BACKGROUND
Balneotherapy, although not a well-established dermatological treatment, is thought to have therapeutic properties for psoriasis and is used as an alternative treatment modality throughout the world.
OBJECTIVE
To evaluate the mechanism underlying the therapeutic immunologic effects of thermomineral water.
METHODS
A murine model of imiquimod-induced psoriasis-like skin inflammation was used for evaluating the therapeutic effects of balneotherapy with Hae-Un-Dae hot spring mineral water. The clinical improvements were evaluated by a dermatologist. Lesional cytokines, including interleukin (IL)-17A, IL-23, and IL-22, were quantitatively measured by real-time reverse transcriptase polymerase chain reaction. Serum levels of interferon-gamma, IL-4, IL-5, and IL-17A were measured by enzyme-linked immunosorbent assay. T cell proportions in the spleen were evaluated by flow cytometry, and histopathological evaluation of the skin was also performed.
RESULTS
The mineral water balneotherapy group showed faster improvement in skin erythema and scales than the distilled water bathing group. A substantial reduction was observed in the lesional mRNA levels of IL-17A and IL-23 in the mineral water group. Serum levels of IL-4 and IL-5 were significantly decreased in the mineral water group but not in the distilled water group. Normalized T cell proportions were observed after bathing.
CONCLUSION
Balneotherapy showed immunomodulatory effects in a psoriasis-like murine model. Balneotherapy suppressed lesional IL-23 and IL-17A, which are important cytokines in the pathogenesis of psoriasis. These results suggest that balneotherapy can be used as an effective and safe treatment for psoriasis.

Keyword

Bath; Immunomodulation; Mineral waters; Psoriasis

MeSH Terms

Balneology*
Baths
Cytokines
Enzyme-Linked Immunosorbent Assay
Erythema
Flow Cytometry
Hot Springs
Immunomodulation
Inflammation
Interferon-gamma
Interleukin-17
Interleukin-23
Interleukin-4
Interleukin-5
Interleukins
Mineral Waters
Psoriasis
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger
Skin
Spleen
Water*
Weights and Measures
Cytokines
Interferon-gamma
Interleukin-17
Interleukin-23
Interleukin-4
Interleukin-5
Interleukins
Mineral Waters
RNA, Messenger
Water

Figure

  • Fig. 1 Clinical improvement of imiquimod-induced psoriasis-like skin lesions during 2 weeks of balneotherapy with distilled water or Hae-Un-Dae hot spring mineral water. IMQ: imiquimod, DW: distilled water, MW: mineral water.

  • Fig. 2 Clinical improvement scores for skin erythema (A) and scales (B). IMQ: imiquimod, DW: distilled water, MW: mineral water.

  • Fig. 3 Expressions of IL-17A, IL-23, and IL-22 mRNA in the skin. IMQ: imiquimod, DW: distilled water, MW: mineral water, IL: interleukin.

  • Fig. 4 Serum levels of IFN-γ (A), IL-4 (B), IL-5 (C), and IL-17A (D). IMQ: imiquimod, DW: distilled water, MW: mineral water, INF: interferon, IL: interleukin. *p<0.05; bar: standard error.

  • Fig. 5 Fluorescence-activated Cell Sorter analysis of splenic T cell profiles. Th1, Th2, Th17, and Foxp3+ Treg. IMQ: imiquimod, DW: distilled water, MW: mineral water. *p<0.05; bar: standard error.

  • Fig. 6 Histological evaluation and comparison of epidermal thickness (H&E, ×100). (A) Imiquimod-induced skin lesion, (B) group treated with distilled water, (C) group treated with mineral water, and (D) negative control group treated with vaseline.

  • Fig. 7 Comparison of epidermal thickness. IMQ: imiquimod, DW: distilled water, MW: mineral water. *p<0.05; bar: standard error.


Cited by  2 articles

Immunomodulatory Effects of Deokgu Thermomineral Water Balneotherapy on Oxazolone-Induced Atopic Dermatitis Murine Model
Young Bok Lee, Su Jin Kim, Sae Mi Park, Kyung Ho Lee, Hyung Jin Han, Dong Soo Yu, So Youn Woo, Seong Taek Yun, Se-Yeong Hamm, Hong Jig Kim, Jin-Wou Kim
Ann Dermatol. 2016;28(2):192-198.    doi: 10.5021/ad.2016.28.2.192.

Investigation of Immune-Regulatory Effects of Mageumsan Hot Spring via Protein Microarray In Vitro
Hyung Jin Hahn, Jung Soo Kim, Yeong Ho Kim, Young Bok Lee, Dong Soo Yu, Jin-Wou Kim
Ann Dermatol. 2018;30(3):322-330.    doi: 10.5021/ad.2018.30.3.322.


Reference

1. Halevy S, Sukenik S. Different modalities of spa therapy for skin diseases at the Dead Sea area. Arch Dermatol. 1998; 134:1416–1420.
Article
2. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009; 361:496–509.
Article
3. Langenbruch AK, Radtke MA, Augustin M. Quality of psoriasis care from the patients' perspective--results of the national health care study PsoReal. Eur J Dermatol. 2012; 22:518–524.
Article
4. Harari M, Czarnowicki T, Fluss R, Ruzicka T, Ingber A. Patients with early-onset psoriasis achieve better results following Dead Sea climatotherapy. J Eur Acad Dermatol Venereol. 2012; 26:554–559.
Article
5. Kudish AI, Harari M, Evseev EG. The measurement and analysis of normal incidence solar UVB radiation and its application to the photoclimatherapy protocol for psoriasis at the Dead Sea, Israel. Photochem Photobiol. 2011; 87:215–222.
Article
6. Klein A, Schiffner R, Schiffner-Rohe J, Einsele-Krämer B, Heinlin J, Stolz W, et al. A randomized clinical trial in psoriasis: synchronous balneophototherapy with bathing in Dead Sea salt solution plus narrowband UVB vs. narrowband UVB alone (TOMESA-study group). J Eur Acad Dermatol Venereol. 2011; 25:570–578.
Article
7. Peroni A, Gisondi P, Zanoni M, Girolomoni G. Balneotherapy for chronic plaque psoriasis at Comano spa in Trentino, Italy. Dermatol Ther. 2008; 21:Suppl 1. S31–S38.
Article
8. Tabolli S, Calza A, Di Pietro C, Sampogna F, Abeni D. Quality of life of psoriasis patients before and after balneo -- or balneophototherapy. Yonsei Med J. 2009; 50:215–221.
Article
9. Cozzi F, Lazzarin P, Todesco S, Cima L. Hypothalamic-pituitary-adrenal axis dysregulation in healthy subjects undergoing mud-bath applications. Arthritis Rheum. 1995; 38:724–726.
Article
10. van der Fits L, Mourits S, Voerman JS, Kant M, Boon L, Laman JD, et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol. 2009; 182:5836–5845.
Article
11. Chae GT, Yun ST, Mayer B, Kim KH, Kim SY, Kwon JS, et al. Fluorine geochemistry in bedrock groundwater of South Korea. Sci Total Environ. 2007; 385:272–283.
Article
12. Ledo E. Mineral water and spas in Spain. Clin Dermatol. 1996; 14:641–646.
Article
13. Picoto A. Mineral water and spas in Portugal. Clin Dermatol. 1996; 14:637–639.
Article
14. Hann SK. Mineral water and spas in Korea. Clin Dermatol. 1996; 14:633–635.
Article
15. Andreassi L, Flori L. Mineral water and spas in Italy. Clin Dermatol. 1996; 14:627–632.
Article
16. Wolf R. Mineral water and spas in Israel. Clin Dermatol. 1996; 14:619–626.
Article
17. Katsambas A, Antoniou C. Mineral water and spas in Greece. Clin Dermatol. 1996; 14:615–618.
Article
18. Titzmann T, Balda BR. Mineral water and spas in Germany. Clin Dermatol. 1996; 14:611–613.
Article
19. Karam P. Mineral water and spas in France. Clin Dermatol. 1996; 14:607–610.
Article
20. Vassileva S. Mineral water and spas in Bulgaria. Clin Dermatol. 1996; 14:601–605.
Article
21. Benedetto AV, Millikan LE. Mineral water and spas in the United States. Clin Dermatol. 1996; 14:583–600.
Article
22. Matz H, Orion E, Wolf R. Balneotherapy in dermatology. Dermatol Ther. 2003; 16:132–140.
Article
23. Merial-Kieny C, Castex-Rizzi N, Selas B, Mery S, Guerrero D. Avène Thermal Spring Water: an active component with specific properties. J Eur Acad Dermatol Venereol. 2011; 25:Suppl 1. 2–5.
Article
24. Piskin G, Sylva-Steenland RM, Bos JD, Teunissen MB. In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin. J Immunol. 2006; 176:1908–1915.
Article
25. Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, et al. Psoriasis Study Group. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med. 2010; 2:52ra72.
Article
26. Kimball AB, Gordon KB, Langley RG, Menter A, Chartash EK, Valdes J. ABT-874 Psoriasis Study Investigators. Safety and efficacy of ABT-874, a fully human interleukin 12/23 monoclonal antibody, in the treatment of moderate to severe chronic plaque psoriasis: results of a randomized, placebo-controlled, phase 2 trial. Arch Dermatol. 2008; 144:200–207.
Article
27. Portalès P, Ariès MF, Licu D, Pinton J, Hernandez-Pion C, Gall Y, et al. Immunomodulation induced by Avène spring water on Th1- and Th2-dependent cytokine production in healthy subjects and atopic dermatitis patients. Skin Pharmacol Appl Skin Physiol. 2001; 14:234–242.
Article
28. Lee HP, Choi YJ, Cho KA, Woo SY, Yun ST, Lee JT, et al. Effect of spa spring water on cytokine expression in human keratinocyte HaCaT cells and on differentiation of CD4(+) T cells. Ann Dermatol. 2012; 24:324–336.
Article
29. Tang Q, Bluestone JA. The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nat Immunol. 2008; 9:239–244.
Article
30. Valitutti S, Castellino F, Musiani P. Effect of sulfurous (thermal) water on T lymphocyte proliferative response. Ann Allergy. 1990; 65:463–468.
31. Halevy S, Giryes H, Friger M, Grossman N, Karpas Z, Sarov B, et al. The role of trace elements in psoriatic patients undergoing balneotherapy with Dead Sea bath salt. Isr Med Assoc J. 2001; 3:828–832.
32. Shani J, Barak S, Ram M, Levi D, Pfeifer Y, Schlesinger T, et al. Serum bromine levels in psoriasis. Pharmacology. 1982; 25:297–307.
Article
33. Cézanne L, Gaboriau F, Charveron M, Morlière P, Tocanne JF, Dubertret L. Effects of the Avène spring water on the dynamics of lipids in the membranes of cultured fibroblasts. Skin Pharmacol. 1993; 6:231–240.
Article
34. Dal Pra I, Chiarini A, Pacchiana R, Zumiani G, Zanoni M, Armato U. Comano's (Trentino) thermal water interferes with tumour necrosis factor-alpha expression and interleukin-8 production and secretion by cultured human psoriatic keratinocytes: yet other mechanisms of its anti-psoriatic action. Int J Mol Med. 2007; 19:373–379.
35. Chiarini A, Dal Pra I, Pacchiana R, Zumiani G, Zanoni M, Armato U. Comano's (Trentino) thermal water interferes with interleukin-6 production and secretion and with cytokeratin-16 expression by cultured human psoriatic keratinocytes: further potential mechanisms of its anti-psoriatic action. Int J Mol Med. 2006; 18:1073–1079.
Article
36. Chiarini A, Dal Pra I, Pacchiana R, Menapace L, Zumiani G, Zanoni M, et al. Comano's (Trentino) thermal water interferes with the expression and secretion of vascular endothelial growth factor-A protein isoforms by cultured human psoriatic keratinocytes: a potential mechanism of its anti-psoriatic action. Int J Mol Med. 2006; 18:17–25.
Article
37. Castex-Rizzi N, Charveron M, Merial-Kieny C. Inhibition of TNF-alpha induced-adhesion molecules by Avène Thermal Spring Water in human endothelial cells. J Eur Acad Dermatol Venereol. 2011; 25:Suppl 1. 6–11.
Article
38. Boisnic S, Branchet-Gumila MC, Segard C. Inhibitory effect of Avene spring water on vasoactive intestinal peptide-induced inflammation in surviving human skin. Int J Tissue React. 2001; 23:89–95.
39. Tsoureli-Nikita E, Menchini G, Ghersetich I, Hercogova J. Alternative treatment of psoriasis with balneotherapy using Leopoldine spa water. J Eur Acad Dermatol Venereol. 2002; 16:260–262.
Article
Full Text Links
  • AD
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr