Influence of topical immunosuppressive therapy with tacrolimus on local immune response in skin of atopic dermatitis patients



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Abstract

Background. To study tacrolimus 0,1% ointment influence on the skin local immune parameters in patients with moderate and severe atopic dermatitis (AD). Materials and methods. The study included 30 patients with moderate (n=20) and severe (n=10) AD. All patients underwent a topical continuous course of treatment with tacrolimus 0,1% ointment twice a day for 14 days. The clinical efficacy of tacrolimus 0,1% ointment was evaluated by the change of the following parameters: SCORAD index, Investigator Global Assessment (IGA) before and after the treatment. All patients underwent a study of local immune response before and after the treatment with the assessment of the expression of IL4, IL5, IL7, IL8, IL10, IL17A, IL23, IL23, IFNγ TGFB1, FOXP3 genes in irritated and treated skin lesions obtained by biopsy. Results. Positive clinical effect - reduction of infiltration, papular rash, dryness, intensity of itch, reflected in the significant decreasing of SCORAD index and IGA was found. The significant decreasing of TGFß (p=0,043308) and IL8 (p=0,038867) gene expression level was revealed, TGFβ and IL8 are the markers of chronic inflammation in atopic dermatitis. The decrease of these parameters during the topical tacrolimus treatment demonstrates local immune response changes in the skin, accompanied by improvement of AD symptoms. Conclusion. The study showed clinical efficacy as well as immunosuppressive activity of tacrolimus 0,1% ointment in patients with moderate and severe AD represented in decreasing of proinflammatory cytokines gene expression TGFβ and IL8 in skin lesions.

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About the authors

O G Elisyutina

Institute of Immunology

Email: el-olga@yandex.ru

E S Fedenko

Institute of Immunology

M N Boldyreva

Institute of Immunology

V V Kadochnikova

Institute of Immunology

References

  1. Аллергология и иммунология: национальное руководство. Под ред. Р.М. Хаитова, Н.И. Ильиной. М.: ГЭОТАР-Медиа: 2009, 656 с.
  2. Bieber Thomas. Mechanisms of disease Atopic Dermatitis. N. Engl. J. Med. 2008, v. 358, p. 1483-1494.
  3. Weidinger S., Novak N. Atopic dermatitis. Lancet. 2016, v. 387, p. 1109-1122.
  4. Homey B., Steinhoff M., Ruzicka T., Leung D.Y. Cytokines and chemokines orchestrate atopic skin inflammation. J. Allergy Clin. Immunol. 2006, v. 118, p. 178-189.
  5. Ozkaya E. Adult-onset atopic dermatitis. J. Am. Acad. Dermatol. 2005, v. 52, p. 579-582.
  6. Lee J., Noh G., Lee S. et al. Atopic dermatitis and cytokines: recent patents in immunoregulatory and therapeutic implications of cytokines in atopic dermatitis - part I: cytokines in atopic dermatitis. Recent Pat. Inflamm. Allergy Drug. Discov. 2012, v. 6 (3), p. 222-247.
  7. Agraval R., Wisniewski J.A., Woodfolk J.A. The role of regulatory T-cells in atopic dermatitis. Curr. Probl. Dermatol. 2011, v. 41, p. 112-124.
  8. Gros E., Bussmann C., Bieber T et al. Expression of chemokines and chemokine receptors in lesional and nonlesional upper skin of patients with atopic dermatitis. J. Allergy Clin. Immunol. 2009, v. 124, p. 753-760.
  9. Gros E., Petzold S., Maintz L. et al. Reduced IFN-γ receptor expression and attenuated IFN-y response by dendritic cells in patients with atopic dermatitis. J. Allergy Clin. Immunol. 2011, v. 128, p. 1015-1021.
  10. Филимонова Т.М., Елисютина О.Г., Феденко Е.С. и соавт. Влияние топических глюкокортикостероидов на экспрессию генов цитокинов в коже и периферической крови больных атопическим дерматитом. Рос. Аллергол. Журн. 2011, № 3, с. 19-30.
  11. Bourmenskaya O., Shubina E., Trofimov D. et al. Host gene expression profiling of cervical smear is eligible for cancer risk evaluation. Journal of Clinical Pathology. 2013, v. 66, p. 282-285.
  12. Qureshi M.A.A., Ahmed A.S., Li J. et al. Validation of Reference Genes for mRNA Quantification in Adjuvant Arthritis. Open Journal of Rheumatology and Autoimmune Diseases. 2012, v. 2, p. 64-72.
  13. Ring J., Alomar A., Bieber T et al. Guidelines for treatment of atopic eczema (atopic dermatitis). Part I. J. Eur. Acad. Dermatol. Venereol. 2012, v. 26, p. 1045-1060.
  14. Ring J., Alomar A., Bieber T et al. Guidelines for treatment of atopic eczema (atopic dermatitis). Part II. J. Eur. Acad. Dermatol. Venereol. 2012, v. 26 (8), p. 1176-1193.
  15. Sidbury R., Davis D.M., Cohen D.E. et al. Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents. J. Am. Acad. Dermatol. 2014, v. 71, p. 327-349.
  16. Boguniewicz M., Fiedler V.C., Raimer S. et al. A randomized, vehicle-controlled trial of tacrolimus ointment for treatment of atopic dermatitis in children. Pediatric Tacrolimus Study Group. J. Allergy Clin. Immunol. 1998, v. 102, p. 637-644.
  17. El-Batawy M.M., Bosseila M.A., Mashaly H.M., Hafez V.S. Topical calcineurin inhibitors in atopic dermatitis: a systematic review and meta-analysis. J. Dermatol. Sci. 2009, v. 54, p. 76-87.
  18. Pucci N., Novembre E., Cammarata M. et al. Scoring atopic dermatitis in infants and young children: distinctive features of SCORAD index. Allergy. 2005, v. 60, p. 113-116.
  19. Eichenfield L.F., Tom W.L., Chamlin S.L. et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J. Am. Acad. Dermatol. 2014, v. 70, p. 338-351.
  20. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 1987, v. 162, p. 156-159.
  21. Hanifin J.M., Ling M.R., Langley R. et al. Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part I, efficacy. J. Am. Acad. Dermatol. 2001, v. 44, p. 28-38.
  22. Doss N., Reitamo S., Dubertret L. et al. Superiority of tacrolimus 0.1% ointment compared with fluticasone 0.005% in adults with moderate to severe atopic dermatitis of the face: results from a randomized, double-blind trial. Br. J. Dermatol. 2009, v. 161, p. 427-434.
  23. Peng W., Novak N. Pathogenesis of atopic dermatitis. Clin. Exp. Allergy. 2015, v. 45, p. 566-574.
  24. Zheng M., Sun G., Mrowietz U. The chemotactic activity of T-lymphocytes in response to interleukin 8 is significantly decreased in patients with psoriasis and atopic dermatitis. Exp. Dermatol. 1996, v. 5, p. 334-340.
  25. Amarbayasgalan T., Takahashi H., Dekio I., Morita E. Interleukin-8 content in the stratum corneum as an indicator of the severity of inflammation in the lesions of atopic dermatitis. Int. Arch. Allergy Immunol. 2013, v. 160, p. 63-74.
  26. Commins S., Borish L., Steinke J. Immunologic messenger molecules: Cytokines, interferons, and chemokines. J. Allergy Clin. Immunol. 2010, v. 125, p. 53-72.
  27. Li A.G., Wang D., Feng X.H., Wang X.J. Latent TGFbeta1 overexpression in keratinocytes results in a severe psoriasis-like skin disorder. EMBO. J. 2004, v. 23, p. 1770-1781.
  28. Варламов E.E., Виноградова T.B., Чусляева A.A., Пампура А.Н. Биомаркеры аллергического воспаления и тяжесть атопического дерматита у детей. Рос. Аллергол. Журн. 2012, № 5, с. 31-35.

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