<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" 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" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">mimmun</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинская иммунология</journal-title><trans-title-group xml:lang="en"><trans-title>Medical Immunology (Russia)</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1563-0625</issn><issn pub-type="epub">2313-741X</issn><publisher><publisher-name>SPb RAACI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.15789/1563-0625-BCP-2214</article-id><article-id custom-type="elpub" pub-id-type="custom">mimmun-2419</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>МАТЕРИАЛЫ ФОРУМА "ДНИ ИММУНОЛОГИИ В СПБ" 2021</subject></subj-group></article-categories><title-group><article-title>ЦИТОКИНОВЫЙ ПРОФИЛЬ В КРОВИ И РЕПАРАЦИЯ В ОЧАГЕ ПОВРЕЖДЕНИЯ В ДИНАМИКЕ ЭКСПЕРИМЕНТАЛЬНОЙ ТЕРМИЧЕСКОЙ ТРАВМЫ В УСЛОВИЯХ ЛОКАЛЬНОГО ИЛИ СИСТЕМНОГО ПРИМЕНЕНИЯ МЕЛАТОНИНА</article-title><trans-title-group xml:lang="en"><trans-title>BLOOD CYTOKINE PROFILE AND LESION SITE REPAIR IN DYNAMICS OF EXPERIMENTAL THERMAL TRAUMA AFTER LOCAL AND SYSTEMIC MELATONIN ADMINISTRATION</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Осиков</surname><given-names>М. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Osikov</surname><given-names>M. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д.м.н., профессор, заведующий кафедрой патологической физиологии,</p><p>454092, г. Челябинск, ул. Воровского, 64</p></bio><bio xml:lang="en"><p>PhD, MD (Medicine), Professor, Head, Department of Pathological Physiology,</p><p>454092, Chelyabinsk, Vorovsky str., 64</p></bio><email xlink:type="simple">prof.osikov@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Агеева</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Ageeva</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>ассистент кафедры патологической физиологии,</p><p>454092, г. Челябинск, ул. Воровского, 64</p></bio><bio xml:lang="en"><p>Assistant Professor, Department of Pathological Physiology,</p><p>454092, Chelyabinsk, Vorovsky str., 64</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБОУ ВО «Южно-Уральский государственный медицинский университет» Министерства здравоохранения РФ</institution><country>Россия</country></aff><aff xml:lang="en"><institution>South Ural State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2021</year></pub-date><pub-date pub-type="epub"><day>18</day><month>10</month><year>2021</year></pub-date><volume>23</volume><issue>4</issue><fpage>705</fpage><lpage>710</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Осиков М.В., Агеева А.А., 2021</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="ru">Осиков М.В., Агеева А.А.</copyright-holder><copyright-holder xml:lang="en">Osikov M.V., Ageeva A.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.mimmun.ru/mimmun/article/view/2419">https://www.mimmun.ru/mimmun/article/view/2419</self-uri><abstract><p>Ожоговый травматизм представляет одну из ключевых медико-социальных проблем. Несмотря на значительные достижения в комбустиологии, медленное заживление и присоединение инфекции составляют ключевые проблемы у ожоговых больных, приводящие к удлинению сроков госпитализации, снижению качества жизни и эмоциональным расстройствам. До 70% всех осложнений после термической травмы (ТТ) связаны с инфекцией – это, прежде всего, пневмония, инфекции мочевыводящих путей. Формирование инфекционных осложнений, включая сепсис, после ТТ связывают с избыточными иммуносупрессивными реакциями, в том числе как компенсацию на длительный, устойчивый провоспалительный ответ, в частности обусловленными гиперпродукцией и эффектами IL-10, IL-4, TGF-β. Цель работы: изучить влияние системного и локального в составе оригинальной дермальной пленки (ДП) применения МТ на показатели репарации и концентрацию в сыворотке некоторых цитокинов в динамике экспериментальной ТТ. Работа выполнена на 84 крысах – самцах линии Wistar массой 240±20 г, которые случайным образом разделены на 4 группы: группа 1 (n = 12) – интактный контроль, группа 2 (n = 30) – животные с ТТ, группа 3 (n = 21) – животные с ТТ и наложением ДП с МТ на область ожога, группа 4 (n = 21) – животные с ТТ и внутрибрюшинным введением МТ. Для моделирования ТТ IIIА степени и относительной площадью 3,5% изолированный участок кожи межлопаточной области погружали в дистиллированную воду с температурой 98-990 С на 12 с. ДП с МТ (в концентрации 0,005 г/г) площадью 12 см2 в группе 3 наносили сразу после ТТ, закрепляя асептической повязкой, перевязку осуществляли ежедневно в течение 5 суток. Внутрибрюшинно вводили МТ ежедневно в дозе 10 мг/кг в течение 5 суток. На 5-е, 10-е и 20-е сутки от момента индукции ТТ вычисляли площадь раны, скорость эпителизации в сыворотке определяли концентрацию интерлейкина-4 (IL-4), фактора некроза опухолей альфа (TNFα), интерферона-гамма (IFNγ). При экспериментальной ТТ в динамике наблюдений от 5-х к 20-м суткам уменьшается абсолютная и относительная площадь раневого дефекта, в связи с чем прогрессивно увеличивается скорость эпителизации раны и доля уменьшения ее площади, на 5-е, 10-е и 20-е сутки в сыворотке увеличивается концентрация TNFα и IL-4 с максимальными значениями на 10-е сутки наблюдения. Локальное применение МТ в составе ДП при ТТ ускоряет заживление ожоговой раны и снижает в сыворотке концентрацию TNFα и IL-4 на 5-е, 10-е и 20-е сутки. Внутрибрюшинное применение МТ при ТТ ускоряет заживление ожоговой раны и снижает в сыворотке концентрацию TNFα на 10-е и 20-е сутки. Ускоряющий репарацию эффект МТ при ТТ более выражен при локальном применении в составе ДП по сравнению с внутрибрюшинным введением. </p></abstract><trans-abstract xml:lang="en"><p>Burn injuries are one of the key medical and social problems. Despite the significant achievements in combustiology, the slow healing and the appearance of infection are the key problems in burn patients, which lead to a longer hospitalization period, to reduction of life quality and to emotional disorders. Up to 70% of all complications after thermal trauma (TT) are connected with infection – first of all, pneumonia, infections of urinal tract. The forming of infectious complications, including sepsis, after TT is associated with excessive immunosuppressive reactions, as compensation for a long, stable proinflammatory response, in particular, owing to hyperproduction and effects of IL-10, IL-4, TGF-β. Aim: to study the influence of systemic and local usage of MT with original dermal film (DF) on reparation and serum cytokine concentration indicators in dynamics of experimental TT. The study was conducted using 84 rats – males of Wistar line, which were divided randomly into 4 groups: 1st group (n = 12) – intact monitoring, 2nd group (n = 30) – animals with TT, 3rd group (n = 21) – animals with TT and DF with MT use on the region of burn, 4th group (n = 21) – animals with TT and intraperitoneal injection of MT. To model TT of IIIA degree and relative area 3,5%, isolated skin area of interscapular area was immersed in distilled water at a temperature of 98-99 °С at 12 s. The DF with MT (at a concentration of 0.005 g/g) on 12 sm2 – area in 3rd group was used daily for 5 days. The MT was injected intraperitoneally daily at the dose of 10 mg/kg for 5 days. The wound area was calculated, the interleukin-4 (IL-4), tumor necrosis factor alpha (TNFα), interferon-gamma (IFNγ) were determined in serum on 5th,10th and 20th day from the moment of TT induction in each group. During experimental TT in dynamic monitoring from 5th to 20th day the absolute and relative areas of wound defect are reduced, because of that the epithelization speed and its part of area reduction are progressively increasing, on 5th,10th and 20th day the concentration of TNFα and IL-4 in serum is increasing with maximum values on 10th day of monitoring. Local usage of MT in DF during TT accelerates the healing of burn wound and lowers the TNFα and IL-4 concentration in serum on 5th, 10th and 20th day. Intraperitoneal use of MT during TT accelerates the healing of burn wound and lowers the TNFα and IL-4 concentration in serum on 5th and 20th day. The reparation accelerating effect of MT during TT is more expressed in locale usage in DF rather than using intraperitoneal injection. </p></trans-abstract><kwd-group xml:lang="ru"><kwd>термическая травма</kwd><kwd>мелатонин</kwd><kwd>репарация</kwd><kwd>цитокины</kwd><kwd>TNFα</kwd><kwd>IFNγ</kwd><kwd>IL-4</kwd></kwd-group><kwd-group xml:lang="en"><kwd>thermal trauma</kwd><kwd>melatonin</kwd><kwd>reparation</kwd><kwd>cytokine</kwd><kwd>TNFα</kwd><kwd>IFNγ</kwd><kwd>IL-4</kwd></kwd-group><funding-group><funding-statement xml:lang="en">The study was carried with support of the Federal State Budgetary Institution “Fund for assistance to the development of small forms of enterprises in the scientific and technical sphere” under the program U. M. N. I. K. (agreement No. 15583GU/2020, dated of 05.07.2020). The research study was funded by the RFBR and Chelyabinsk Region, Project No. 20-415-740016.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Boutin J.A., Ferry G. Is there sufficient evidence that the melatonin binding Site MT3 is Quinone Reductase 2? J. Pharmacol. Exp. Ther., 2019, no. 368, pp. 59–65. doi:10.1124/jpet.118.253260.</mixed-citation><mixed-citation xml:lang="en">Boutin J.A., Ferry G. Is there sufficient evidence that the melatonin binding Site MT3 is Quinone Reductase 2? J. Pharmacol. Exp. Ther., 2019, no. 368, pp. 59–65. doi:10.1124/jpet.118.253260.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Dong K., Goyarts E., Rella A., Pelle E., Wong Y.H., Pernodet N. Age associated decrease of MT-1 melatonin receptor in human dermal skin fibroblasts impairs protection against UV-induced DNA damage. Int. J. Mol. Sci., 2020, Vol. 21, no. 1, pp. E326. doi: 10.3390/ijms21010326.</mixed-citation><mixed-citation xml:lang="en">Dong K., Goyarts E., Rella A., Pelle E., Wong Y.H., Pernodet N. Age associated decrease of MT-1 melatonin receptor in human dermal skin fibroblasts impairs protection against UV-induced DNA damage. Int. J. Mol. Sci., 2020, Vol. 21, no. 1, pp. E326. doi: 10.3390/ijms21010326.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Favero G., Franceschetti L., Bonomini F., et al. Melatonin as an anti-inflammatory agent modulating inflammasome activation. Int. J. Endocrinol., 2017, no. 2017, pp. 1835195. doi: 10.1155/2017/1835195.</mixed-citation><mixed-citation xml:lang="en">Favero G., Franceschetti L., Bonomini F., et al. Melatonin as an anti-inflammatory agent modulating inflammasome activation. Int. J. Endocrinol., 2017, no. 2017, pp. 1835195. doi: 10.1155/2017/1835195.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Galano A., Tan D.X., Reiter R.J. Melatonin: a versatile protector against oxidative DNA damage. Molecules, 2018, no. 23, pp. E530. doi:10.3390/molecules23030530.</mixed-citation><mixed-citation xml:lang="en">Galano A., Tan D.X., Reiter R.J. Melatonin: a versatile protector against oxidative DNA damage. Molecules, 2018, no. 23, pp. E530. doi:10.3390/molecules23030530.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Hardeland R. Aging, melatonin, and the pro- and anti-inflammatory networks. Int. J. Mol. Sci., 2019, Vol. 20, no. 5, pii: 1223. doi:10.3390/ijms20051223.</mixed-citation><mixed-citation xml:lang="en">Hardeland R. Aging, melatonin, and the pro- and anti-inflammatory networks. Int. J. Mol. Sci., 2019, Vol. 20, no. 5, pii: 1223. doi:10.3390/ijms20051223.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Lateef Z., Stuart G., Jones N., Mercer A., Fleming S., Wise L. The cutaneous inflammatory response to thermal burn injury in a murine model. Int. J. Mol. Sci., 2019, Vol. 20, no. 3, pii: E538. doi: 10.3390/ijms20030538</mixed-citation><mixed-citation xml:lang="en">Lateef Z., Stuart G., Jones N., Mercer A., Fleming S., Wise L. The cutaneous inflammatory response to thermal burn injury in a murine model. Int. J. Mol. Sci., 2019, Vol. 20, no. 3, pii: E538. doi: 10.3390/ijms20030538</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Loynes C.A., Lee J.A., Robertson A.L., Steel M.J., Ellett F., Feng Y., Levy B.D., Whyte M.K., Renshaw S.A. PGE2 production at sites of tissue injury promotes an anti-inflammatory neutrophil phenotype and determines the outcome of inflammation resolution in vivo. Sci. Adv., 2018, no. 4, pp. eaar8320. doi:10.1126/sciadv.aar8320.</mixed-citation><mixed-citation xml:lang="en">Loynes C.A., Lee J.A., Robertson A.L., Steel M.J., Ellett F., Feng Y., Levy B.D., Whyte M.K., Renshaw S.A. PGE2 production at sites of tissue injury promotes an anti-inflammatory neutrophil phenotype and determines the outcome of inflammation resolution in vivo. Sci. Adv., 2018, no. 4, pp. eaar8320. doi:10.1126/sciadv.aar8320.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Mayo J.C., Aguado A., Cernuda-Cernuda R., Alvarez-Artime A., Cepas V., Quiros-Gonzalez I., et al. Melatonin uptake by cells: an answer to its relationship with glucose? Molecules, 2018, no. 23, pp. e1999. doi:10.3390/molecules23081999.</mixed-citation><mixed-citation xml:lang="en">Mayo J.C., Aguado A., Cernuda-Cernuda R., Alvarez-Artime A., Cepas V., Quiros-Gonzalez I., et al. Melatonin uptake by cells: an answer to its relationship with glucose? Molecules, 2018, no. 23, pp. e1999. doi:10.3390/molecules23081999.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Nishiguchi T., Ito I., Lee J.O., Suzuki S., Suzuki F., Kobayashi M. Macrophage polarization and MRSA infection in burned mice. Immunol. Cell Biol, 2017, Vol. 95, no. 2, pp. 198-206. doi:10.1038/icb.2016.84.</mixed-citation><mixed-citation xml:lang="en">Nishiguchi T., Ito I., Lee J.O., Suzuki S., Suzuki F., Kobayashi M. Macrophage polarization and MRSA infection in burned mice. Immunol. Cell Biol, 2017, Vol. 95, no. 2, pp. 198-206. doi:10.1038/icb.2016.84.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Osikov M.V., Simoyan E.V., Saedgalina O.T. Effect of erythropoietin on the quantitative composition and apoptosis of lymphocytes of peripheral blood in dynamic of experimental thermal injury. Russian Journal of Immunology, 2016, Vol. 10 (19), no. 2-1, pp. 479-481. (In Russ.)</mixed-citation><mixed-citation xml:lang="en">Osikov M.V., Simoyan E.V., Saedgalina O.T. Effect of erythropoietin on the quantitative composition and apoptosis of lymphocytes of peripheral blood in dynamic of experimental thermal injury. Russian Journal of Immunology, 2016, Vol. 10 (19), no. 2-1, pp. 479-481. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Osikov M.V., Simoyan E.V., Saedgalina O.T. Erythropoietin influence in trancedermal film on the indicators of immune status of rat in experimental thermal injury. Experimental and Clinical Pharmacology, 2018, Vol. 81, no. 8, pp. 13-18. (In Russ.)</mixed-citation><mixed-citation xml:lang="en">Osikov M.V., Simoyan E.V., Saedgalina O.T. Erythropoietin influence in trancedermal film on the indicators of immune status of rat in experimental thermal injury. Experimental and Clinical Pharmacology, 2018, Vol. 81, no. 8, pp. 13-18. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Osikov M.V., Simoyan E.V., Saedgalina O.T. Influence of melatonin on innate immunity in experimental desynchronosis under led lighting conditions. Russian Journal of Immunology, 2015, Vol. 9 (18), no, 3-1, pp. 154-156. (In Russ.)</mixed-citation><mixed-citation xml:lang="en">Osikov M.V., Simoyan E.V., Saedgalina O.T. Influence of melatonin on innate immunity in experimental desynchronosis under led lighting conditions. Russian Journal of Immunology, 2015, Vol. 9 (18), no, 3-1, pp. 154-156. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Saavedra P.A., deBrito E.S., Areda C.A., Escalda P.M., Galato D. Burns in the Brazilian Unified Health System: a review of hospitalization from 2008 to 2017. Int. J. Burns Trauma, 2019, Vol. 9, no. 5, pp. 88-98.</mixed-citation><mixed-citation xml:lang="en">Saavedra P.A., deBrito E.S., Areda C.A., Escalda P.M., Galato D. Burns in the Brazilian Unified Health System: a review of hospitalization from 2008 to 2017. Int. J. Burns Trauma, 2019, Vol. 9, no. 5, pp. 88-98.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Slominski A.T., Semak I., Fischer T.W., Kim T.-K., Kleszczyński K., Hardeland R., Reiter R.J. Metabolism of melatonin in the skin: why is it important? Experimental Dermatology, 2017, Vol. 26, no. 7, pp. 563–568. doi:10.1111/exd.13208.</mixed-citation><mixed-citation xml:lang="en">Slominski A.T., Semak I., Fischer T.W., Kim T.-K., Kleszczyński K., Hardeland R., Reiter R.J. Metabolism of melatonin in the skin: why is it important? Experimental Dermatology, 2017, Vol. 26, no. 7, pp. 563–568. doi:10.1111/exd.13208.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Wang Y., Beekman J., Hew J., Jackson S., Issler-Fisher A.C., Parungao R., Lajevardi S.S., Li Z., Maitz P.K.M. Burn injury: challenges and advances in burn wound healing, infection, pain and scarring. Adv. Drug Deliv. Rev., 2018, no. 123, pp. 3-17. doi:10.1016/j.addr.2017.09.018.</mixed-citation><mixed-citation xml:lang="en">Wang Y., Beekman J., Hew J., Jackson S., Issler-Fisher A.C., Parungao R., Lajevardi S.S., Li Z., Maitz P.K.M. Burn injury: challenges and advances in burn wound healing, infection, pain and scarring. Adv. Drug Deliv. Rev., 2018, no. 123, pp. 3-17. doi:10.1016/j.addr.2017.09.018.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
