<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Russian Journal of Allergy</journal-id><journal-title-group><journal-title xml:lang="en">Russian Journal of Allergy</journal-title><trans-title-group xml:lang="ru"><trans-title>Российский Аллергологический Журнал</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1810-8830</issn><issn publication-format="electronic">2686-682X</issn><publisher><publisher-name xml:lang="en">Publishing House ABV Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">310</article-id><article-id pub-id-type="doi">10.36691/RJA310</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Articles</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Статьи</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Influence of topical immunosuppressive therapy with tacrolimus on local immune response in skin of atopic dermatitis patients</article-title><trans-title-group xml:lang="ru"><trans-title>Влияние наружной иммуносупрессивной терапии такролимусом на показатели локального иммунного ответа в коже больных атопическим дерматитом</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Elisyutina</surname><given-names>O G</given-names></name><name xml:lang="ru"><surname>Елисютина</surname><given-names>Ольга Гурьевна</given-names></name></name-alternatives><email>el-olga@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Fedenko</surname><given-names>E S</given-names></name><name xml:lang="ru"><surname>Феденко</surname><given-names>Е С</given-names></name></name-alternatives><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Boldyreva</surname><given-names>M N</given-names></name><name xml:lang="ru"><surname>Болдырева</surname><given-names>М Н</given-names></name></name-alternatives><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Kadochnikova</surname><given-names>V V</given-names></name><name xml:lang="ru"><surname>Кадочникова</surname><given-names>В В</given-names></name></name-alternatives><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Institute of Immunology</institution></aff><aff><institution xml:lang="ru">ФГБУ «ГНЦ Институт иммунологии» ФМБА России</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2017-06-15" publication-format="electronic"><day>15</day><month>06</month><year>2017</year></pub-date><volume>14</volume><issue>3</issue><issue-title xml:lang="en">VOL 14, NO3 (2017)</issue-title><issue-title xml:lang="ru">ТОМ 14, №3 (2017)</issue-title><fpage>27</fpage><lpage>34</lpage><history><date date-type="received" iso-8601-date="2020-03-10"><day>10</day><month>03</month><year>2020</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2017, Pharmarus Print Media</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2017, Фармарус Принт Медиа</copyright-statement><copyright-year>2017</copyright-year><copyright-holder xml:lang="en">Pharmarus Print Media</copyright-holder><copyright-holder xml:lang="ru">Фармарус Принт Медиа</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/" start_date="2019-12-15"/></permissions><self-uri xlink:href="https://rusalljournal.ru/raj/article/view/310">https://rusalljournal.ru/raj/article/view/310</self-uri><abstract xml:lang="en"><p>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.</p></abstract><trans-abstract xml:lang="ru"><p>Цель. Изучить эффективность и влияние наружной иммуносупрессивной терапии такролимусом на показатели локального иммунного ответа в коже больных атопическим дерматитом (АтД). Материалы и методы. В исследование включены 30 больных со среднетяжелым (n=20) и тяжелым АтД (n=10). Всем больным АтД проведен непрерывный курс наружной терапии 0,1% мазью такролимус в течение 14 дней. Пациенты наносили препарат на все пораженные участки кожи 2 раза в день тонким слоем. Клиническую эффективность лечения оценивали по изменению следующих параметров: индекса SCORAD, исследовательской глобальной оценки до и после лечения. Всем больным проведено исследование локального иммунного ответа до и после лечения с оценкой экспрессии генов IL4, IL5, IL7, IL8, IL10, IL17A, IL23, IL23, IFNγ, TGFB1, FOXP3 методом ПЦР в реальном времени в биоптатах кожи, взятой с пораженных участков. Результаты. На фоне терапии у больных АтД отмечен положительный клинический эффект: уменьшение гиперемии, инфильтрации, высыпаний, сухости, интенсивности зуда кожи, что отразилось в достоверном уменьшении значений индексов SCORAD и исследовательской глобальной оценки. При изучении локального иммунного ответа выявлено достоверное уменьшение уровня экспрессии генов TGFβ (p=0,043) и IL8 (p=0,039), которые являются маркерами хронического воспаления при АтД. Уменьшение значения данных показателей на фоне лечения 0,1% мазью такролимус свидетельствует об изменении иммунного ответа в коже, сопровождающегося клиническим облегчением течения АтД. Заключение. Показана клиническая и местная иммунотропная активность 0,1% мази такролимус у больных с тяжелым и среднетяжелым АтД, характеризующаяся клиническим улучшением состояния кожи и уменьшением уровня экспрессии генов провоспалительных цитокинов TGFβ и IL8.</p></trans-abstract><kwd-group xml:lang="en"><kwd>atopic dermatitis</kwd><kwd>topical immunosuppressive therapy</kwd><kwd>topical calcineurin inhibitors</kwd><kwd>tacrolimus</kwd><kwd>local immune response</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>атопический дерматит</kwd><kwd>наружная иммуносупрессивная терапия</kwd><kwd>топические ингибиторы кальциневрина</kwd><kwd>такролимус</kwd><kwd>локальный иммунный ответ</kwd></kwd-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Аллергология и иммунология: национальное руководство. Под ред. Р.М. Хаитова, Н.И. Ильиной. М.: ГЭОТАР-Медиа: 2009, 656 с.</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Bieber Thomas. Mechanisms of disease Atopic Dermatitis. N. Engl. J. Med. 2008, v. 358, p. 1483-1494.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Weidinger S., Novak N. Atopic dermatitis. Lancet. 2016, v. 387, p. 1109-1122.</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>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.</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Ozkaya E. Adult-onset atopic dermatitis. J. Am. Acad. Dermatol. 2005, v. 52, p. 579-582.</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>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.</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>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.</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>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.</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>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.</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>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.</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>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.</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>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.</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>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.</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>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.</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>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.</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>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.</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>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.</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>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.</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>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.</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>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.</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>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.</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>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.</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Peng W., Novak N. Pathogenesis of atopic dermatitis. Clin. Exp. Allergy. 2015, v. 45, p. 566-574.</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>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.</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>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.</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Commins S., Borish L., Steinke J. Immunologic messenger molecules: Cytokines, interferons, and chemokines. J. Allergy Clin. Immunol. 2010, v. 125, p. 53-72.</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>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.</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>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.</mixed-citation></ref></ref-list></back></article>
