<?xml version="1.0"?>
<!DOCTYPE article
PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.4 20190208//EN"
       "JATS-journalpublishing1.dtd">
<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" article-type="research-article" dtd-version="1.4" xml:lang="en">
 <front>
  <journal-meta>
   <journal-id journal-id-type="publisher-id">Actual problems in dentistry</journal-id>
   <journal-title-group>
    <journal-title xml:lang="en">Actual problems in dentistry</journal-title>
    <trans-title-group xml:lang="ru">
     <trans-title>Проблемы стоматологии</trans-title>
    </trans-title-group>
   </journal-title-group>
   <issn publication-format="print">2077-7566</issn>
   <issn publication-format="online">2412-9461</issn>
  </journal-meta>
  <article-meta>
   <article-id pub-id-type="publisher-id">40210</article-id>
   <article-id pub-id-type="doi">10.18481/2077-7566-2020-16-3-18-22</article-id>
   <article-categories>
    <subj-group subj-group-type="toc-heading" xml:lang="ru">
     <subject>ТЕРАПЕВТИЧЕСКАЯ СТОМАТОЛОГИЯ</subject>
    </subj-group>
    <subj-group subj-group-type="toc-heading" xml:lang="en">
     <subject>THERAPEUTIC  DENTISTRY</subject>
    </subj-group>
    <subj-group>
     <subject>ТЕРАПЕВТИЧЕСКАЯ СТОМАТОЛОГИЯ</subject>
    </subj-group>
   </article-categories>
   <title-group>
    <article-title xml:lang="en">ARE SALIVARY CYTOKINES OF THE IL-1 FAMILY BIOMARKERS OF CHRONIC PERIODONTITIS?</article-title>
    <trans-title-group xml:lang="ru">
     <trans-title>ЯВЛЯЮТСЯ ЛИ  САЛИВАРНЫЕ ЦИТОКИНЫ СЕМЕЙСТВА ИЛ-1 БИОМАРКЕРАМИ ХРОНИЧЕСКОГО ПАРОДОНТИТА?</trans-title>
    </trans-title-group>
   </title-group>
   <contrib-group content-type="authors">
    <contrib contrib-type="author">
     <contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0966-9571</contrib-id>
     <name-alternatives>
      <name xml:lang="ru">
       <surname>Базарный</surname>
       <given-names>Владимир Викторович</given-names>
      </name>
      <name xml:lang="en">
       <surname>Bazarnyy</surname>
       <given-names>Vladimir Viktorovich</given-names>
      </name>
     </name-alternatives>
     <email>vlad-bazarny@yandex.ru</email>
     <bio xml:lang="ru">
      <p>доктор медицинских наук;</p>
     </bio>
     <bio xml:lang="en">
      <p>doctor of medical sciences;</p>
     </bio>
     <xref ref-type="aff" rid="aff-1"/>
    </contrib>
    <contrib contrib-type="author">
     <contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4921-7222</contrib-id>
     <name-alternatives>
      <name xml:lang="ru">
       <surname>Полушина</surname>
       <given-names>Лариса Гоергиевна</given-names>
      </name>
      <name xml:lang="en">
       <surname>Polushina</surname>
       <given-names>Larisa Georgievna</given-names>
      </name>
     </name-alternatives>
     <email>polushina-larisa@bk.ru</email>
     <bio xml:lang="ru">
      <p>кандидат медицинских наук;</p>
     </bio>
     <bio xml:lang="en">
      <p>candidate of medical sciences;</p>
     </bio>
     <xref ref-type="aff" rid="aff-1"/>
    </contrib>
    <contrib contrib-type="author">
     <contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0296-8723</contrib-id>
     <name-alternatives>
      <name xml:lang="ru">
       <surname>Семенцова</surname>
       <given-names>Елена Анатольевна</given-names>
      </name>
      <name xml:lang="en">
       <surname>Semencova</surname>
       <given-names>Elena Anatolievna</given-names>
      </name>
     </name-alternatives>
     <email>vanevs@mail.ru</email>
     <bio xml:lang="ru">
      <p>кандидат медицинских наук;</p>
     </bio>
     <bio xml:lang="en">
      <p>candidate of medical sciences;</p>
     </bio>
     <xref ref-type="aff" rid="aff-1"/>
    </contrib>
    <contrib contrib-type="author">
     <contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7592-8343</contrib-id>
     <name-alternatives>
      <name xml:lang="ru">
       <surname>Светлакова</surname>
       <given-names>Елена Николаевна</given-names>
      </name>
      <name xml:lang="en">
       <surname>Svetlakova</surname>
       <given-names>Elena Nikolaevna</given-names>
      </name>
     </name-alternatives>
     <email>svet_anel11@mail.ru</email>
     <bio xml:lang="ru">
      <p>кандидат медицинских наук;</p>
     </bio>
     <bio xml:lang="en">
      <p>candidate of medical sciences;</p>
     </bio>
     <xref ref-type="aff" rid="aff-1"/>
    </contrib>
    <contrib contrib-type="author">
     <contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8439-3272</contrib-id>
     <name-alternatives>
      <name xml:lang="ru">
       <surname>Мандра</surname>
       <given-names>Юлия Владимировна</given-names>
      </name>
      <name xml:lang="en">
       <surname>Mandra</surname>
       <given-names>Yuliya V.</given-names>
      </name>
     </name-alternatives>
     <email>jmandra@mail.ru</email>
     <bio xml:lang="ru">
      <p>доктор медицинских наук;</p>
     </bio>
     <bio xml:lang="en">
      <p>doctor of medical sciences;</p>
     </bio>
     <xref ref-type="aff" rid="aff-2"/>
    </contrib>
   </contrib-group>
   <aff-alternatives id="aff-1">
    <aff>
     <institution xml:lang="ru">Уральский государственный медицинский университет</institution>
    </aff>
    <aff>
     <institution xml:lang="en">Ural State Medical University</institution>
    </aff>
   </aff-alternatives>
   <aff-alternatives id="aff-2">
    <aff>
     <institution xml:lang="ru">Уральский государственный медицинский университет</institution>
     <city>Екатеринбург</city>
     <country>Россия</country>
    </aff>
    <aff>
     <institution xml:lang="en">Ural State Medical University</institution>
     <city>Yekaterinburg</city>
     <country>Russian Federation</country>
    </aff>
   </aff-alternatives>
   <volume>16</volume>
   <issue>3</issue>
   <fpage>18</fpage>
   <lpage>22</lpage>
   <self-uri xlink:href="https://dental-press.ru/en/nauka/article/40210/view">https://dental-press.ru/en/nauka/article/40210/view</self-uri>
   <abstract xml:lang="ru">
    <p>Предмет. В систематических обзорах последних лет обсуждается вопрос о клинической ценности цитокинов семейства интерлейкин-1 (ИЛ-1) при хроническом пародонтите (ХП). Одни авторы считают их  надежными биомаркерами,  другие полагают, что, хотя они и позволяют дифференцировать гингивит и тяжелый ХП,  количество и качество опубликованных работ требуют продолжения исследований в этой области.&#13;
Цель исследования ― оценить клиническую ценность  уровня цитокинов  семейства ИЛ-1   при хроническом пародонтите легкой степени.&#13;
Методология. Все участники исследования были разделены на две группы: основную и контрольную. В основную группу вошли 45 пациентов с хроническим пародонтитом легкой степени, в контрольную ― 32 практически здоровых добровольца без патологии пародонта. Методом мультипараметрического флуоресцентного анализа с магнитными микросферами (хMAP-технология, Luminex) определяли концентрацию ИЛ-1α и ИЛ-1β, ИЛ-18, ИЛ-1RA (антагонист рецептора) в ротовой жидкости. &#13;
Результаты. В группе больных пародонтитом в сравнении с группой контроля наблюдалось повышение в ротовой жидкости уровней ИЛ-1RA в 3,14 раза (р=0,01), ИЛ-1α ― в 2,3 (р=0,02).  Интегральная характеристика клинической ценности параметров (AUC) достаточно высока для обоих показателей: ИЛ-1RA ― 0,91 и ИЛ-1α ― 0,94.  Содержание ИЛ-1β и  ИЛ-18 существенно не менялось. &#13;
Выводы.  В исследовании установлено повышение концентрации саливарных  цитокинов семейства ИЛ-1 при ХП. Клинико-диагностические характеристики таких тестов, как содержание  ИЛ-1α и  IL-1RA в ротовой жидкости, позволяют рассматривать их в качестве биомаркеров хронического пародонтита легкой степени.</p>
   </abstract>
   <trans-abstract xml:lang="en">
    <p>Subject. In recent systematic reviews, the question of the clinical value of cytokines of the interleukin-1 (IL-1) family in chronic periodontitis (CP) has been discussed. Some authors consider them to be reliable biomarkers, while others believe that although they allow differentiating gingivitis and severe CP, the quantity and quality of published works require further research in this area.&#13;
The aim of the study was to evaluate the clinical value of the level of cytokines of the     IL-1 family in chronic mild periodontitis.&#13;
Methodology. All study participants were divided into two groups: main and control. The main group included 45 patients with mild chronic periodontitis, the control group consisted of 32 practically healthy volunteers without periodontal pathology. The concentration of IL-1α and IL-1β, IL-18, IL-1RA (receptor antagonist) in the oral fluid was determined by the method of multiparameter fluorescence analysis with magnetic microspheres (хMAP-technology, Luminex).&#13;
Results. In the group of patients with periodontitis, there was an increase in the oral fluid levels of IL-1RA by 3.14 times (p = 0.01), IL-1α - by 2.3 (p = 0.02) in comparison with the control group. The integral characteristic of the clinical value of the parameters (AUC) is quite high for both indicators: IL-1RA ― 0.91 and IL-1α ― 0.94. The content of IL-1β and IL-18 did not change significantly.&#13;
Conclusions. The study found an increase in the concentration of salivary cytokines of the IL-1 family in CP. Clinical and diagnostic characteristics of such tests as the content of IL-1α and IL-1RA in the oral fluid make it possible to consider them as biomarkers of mild chronic periodontitis.</p>
   </trans-abstract>
   <kwd-group xml:lang="ru">
    <kwd>пародонтит</kwd>
    <kwd>ротовая жидкость</kwd>
    <kwd>интерлейкин-1</kwd>
    <kwd>цитокины</kwd>
    <kwd>диагностическая эффективность</kwd>
   </kwd-group>
   <kwd-group xml:lang="en">
    <kwd>periodontitis</kwd>
    <kwd>oral fluid</kwd>
    <kwd>interleukin-1</kwd>
    <kwd>cytokines</kwd>
    <kwd>diagnostic efficiency</kwd>
   </kwd-group>
  </article-meta>
 </front>
 <body>
  <p></p>
 </body>
 <back>
  <ref-list>
   <ref id="B1">
    <label>1.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Патогенетическое обоснование новых подходов к оценке состояния тканей полости рта при хроническом генерализованном пародонтите / В. В. Базарный, Л. Г. Полушина, А. Ю. Максимова [и др.] // Проблемы стоматологии. - 2018. - Т. 14, № 4. - С. 14-18.</mixed-citation>
     <mixed-citation xml:lang="en">Bazarnyj, V. V., Polushina, L. G., Maksimova, A. Yu. et al. (2018). Patogeneticheskoe obosnovanie novyh podhodov k ocenke sostoyaniya tkanej polosti rta pri hronicheskom generalizovannom parodontite [Pathogenetic substantiation of new approaches to assessing the state of oral tissues in chronic generalized periodontitis]. Problemy stomatologii [Actual problems in dentistry], 14, 4, 14-18. (In Russ.)</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B2">
    <label>2.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Значение некоторых интерлейкинов в патогенезе пародонтита / В. В. Базарный, Л. Г. Полушина, Е. А. Семенцова [и др.] // Вестник Уральской медицинской академической науки. - 2017. - Т. 14, № 1. - С. 35-39.</mixed-citation>
     <mixed-citation xml:lang="en">Bazarnyj, V. V., Polushina L. G., Semencova, E. A. et al. (2017). Znachenie nekotoryh interlejkinov v patogeneze parodontita [The value of some interleukins in the pathogenesis of periodontitis]. Vestnik Ural'skoj medicinskoj akademicheskoj nauki [Bulletin of the Ural Medical Academic Science], 14, 1, 35-39. (In Russ.)</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B3">
    <label>3.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Лабораторно-клиническое обоснование атравматичности использования индивидуального формирователя десны авторской конструкции / П. М. Нерсесян, С. Е. Жолудев, В. В. Базарный [и др.] // Проблемы стоматологии. - 2019. - Т. 15, № 3. - С. 96-102.</mixed-citation>
     <mixed-citation xml:lang="en">Nersesyan. P. M., Zholudev, S. E., Bazarnyj, V. V. et al. (2019). Laboratorno-klinicheskoe obosnovanie atravmatichnosti ispol'zovaniya individual'nogo formirovatelya desny avtorskoj konstrukcii [Laboratory and clinical substantiation of the atraumatic nature of the use of an individual gum shaper of the author's design]. Problemy stomatologii [Actual problems in dentistry], 15, 3, 96-102. (In Russ.)</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B4">
    <label>4.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Орехова, Л. Ю. Местный иммунитет и особенности клинического течения хронического генерализованного катарального гингивита (ХГКГ), ассоциированного с нейроциркуляторной астенией (НЦА) у юношей призывного возраст / Л. Ю. Орехова, М. Г. Пачкория, Н. А. Яманидзе // Проблемы стоматологии. - 2017. - Т. 13, № 3. - С. 36-41.</mixed-citation>
     <mixed-citation xml:lang="en">Orekhova, L. YU., Pachkoriya, M. G., Yamanidze, N. A. (2017). Mestnyj immunitet i osobennosti klinicheskogo techeniya hronicheskogo generalizovannogo kataral'nogo gingivita (HGKG), associirovannogo s nejrocirkulyatornoj asteniej (NCA) u yunoshej prizyvnogo vozrast [Local immunity and clinical features of chronic generalized catarrhal gingivitis (CGCG) associated with neurocirculatory asthenia (NCA) in young men of draft age]. Problemy stomatologii [Actual problems in dentistry], 13, 3, 36-41. (In Russ.)</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B5">
    <label>5.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Клинико-патогенетическое значение некоторых цитокинов при пародонтите / Л. Г. Полушина, Е. Н. Светлакова, Е. А. Семенцова [и др.] // Медицинская иммунология. - 2017. - Т. 19 (6). - С. 803-806.</mixed-citation>
     <mixed-citation xml:lang="en">Polushina, L. G., Svetlakova, E. N., Semencova, E. A. et al (2017). Kliniko-patogeneticheskoe znachenie nekotoryh citokinov pri parodontite [Clinical and pathogenetic significance of some cytokines in periodontitis]. Medicinskaya immunologiya [Medical immunology], 19 (6), 803-806. (In Russ.)</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B6">
    <label>6.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Accuracy of single molecular biomarkers in saliva for the diagnosis of periodontitis: A systematic review and meta-analysis / N. Arias-Bujanda, A. Regueira-Iglesias [et al.] // J Clin Periodontol. - 2020. - Vol. 47 (1). - P. 2-18.</mixed-citation>
     <mixed-citation xml:lang="en">Arias-Bujanda, N., Regueira-Iglesias, A. et al. (2020). Accuracy of single molecular biomarkers in saliva for the diagnosis of periodontitis: A systematic review and meta-analysis. J Clin Periodontol, 47 (1), 2-18.</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B7">
    <label>7.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">The Expanding Family of interleukin-1 Cytokines and Their Role in Destructive Inflammatory Disorders / H. E. Barksby, S. R. Lea, P. M. Preshaw, J. J Taylor // Clin Exp Immunol. - 2007. - Vol. 149 (2). - Р. 217-225.</mixed-citation>
     <mixed-citation xml:lang="en">Barksby, H. E., Lea, S. R., Preshaw, P. M., Taylor, J. J. (2007). The Expanding Family of interleukin-1 Cytokines and Their Role in Destructive Inflammatory Disorders. Clin Exp Immunol, 149 (2), 217-225.</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B8">
    <label>8.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Cardoso, E. L. Chronic periodontitis, inflammatory cytokines, and interrelationship with other chronic diseases / E. L. Cardoso, C. Reis, M. C. Manzanares-Céspedes // Postgrad Med.J. - 2018. - Vol. 130. - Р. 98-104.</mixed-citation>
     <mixed-citation xml:lang="en">Cardoso, E. L., Reis, C., Manzanares-Céspedes, M. C. (2018). Chronic periodontitis, inflammatory cytokines, and interrelationship with other chronic diseases. Postgrad Med.J., 130, 98-104.</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B9">
    <label>9.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Chan, A. H. Inflammasome signaling and regulation of interleukin-1 family cytokines / A. H. Chan, K. Schroder // J Exp Med. - 2020. - Vol. 217 (1).</mixed-citation>
     <mixed-citation xml:lang="en">Chan, A. H., Schroder, K. (2020). Inflammasome signaling and regulation of interleukin-1 family cytokines. J Exp Med, 217 (1).</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B10">
    <label>10.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Interleukin-1β is a potential therapeutic target for periodontitis: a narrative review / К. Cheng, Z. Wu, M. Li, T. Hu // Int J Oral Sci. - 2020. - Vol. 12. - P. 2.</mixed-citation>
     <mixed-citation xml:lang="en">Cheng, K., Wu, Z., Li, M., Hu, T. (2020). Interleukin-1β is a potential therapeutic target for periodontitis: a narrative review. Int J Oral Sci, 12, 2.</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B11">
    <label>11.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Dinarello, C. A. Overview of the IL-1 family in innate inflammation and acquired immunity / C. A. Dinarello // Immunol Rev. - 2018. - № 281 (1). - P. 8-27.</mixed-citation>
     <mixed-citation xml:lang="en">Dinarello, C. A. (2018). Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev, 281 (1), 8-27.</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B12">
    <label>12.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">The effect of scaling and root planning on salivary TNF-α and IL-1 concentrations in patients with chronic periodontitis / M. Eivazi, N. Falahi [et al.] // Open Dent J. - 2017. - Vol. 11.- Р. 573-580.</mixed-citation>
     <mixed-citation xml:lang="en">Eivazi, M., Falahi, N. et al. (2017). The effect of scaling and root planning on salivary TNF-α and IL-1 concentrations in patients with chronic periodontitis. Open Dent J, 11, 573-580.</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B13">
    <label>13.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Porphyromonas gingivalis culture supernatants differentially regulate interleukin-1beta and interleukin-18 in human monocytic cells / M. Hamedi, G. N. Belibasakis, A. T. Cruchley [et al.] // Cytokine. - 2009. - Vol. 45 (2). - Р. 99-104.</mixed-citation>
     <mixed-citation xml:lang="en">Hamedi, M., Belibasakis, G. N., Cruchley, A. T. et al. (2009). Porphyromonas gingivalis culture supernatants differentially regulate interleukin-1beta and interleukin-18 in human monocytic cells. Cytokine, 45 (2), 99-104.</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B14">
    <label>14.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Inflammatory bone loss in experimental periodontitis induced by Aggregatibacter actinomycetemcomitans in interleukin-1 receptor antagonist knockout mice Noguchi / A. Izawa [et al.] // Infect Immun. - 2014. - Vol. 82(5). - Р. 1904-1913.</mixed-citation>
     <mixed-citation xml:lang="en">Izawa, A. et al. (2014). Inflammatory bone loss in experimental periodontitis induced by Aggregatibacter actinomycetemcomitans in interleukin-1 receptor antagonist knockout mice Noguchi. Infect Immun, 82 (5), 1904-1913.</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B15">
    <label>15.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Kc, S. Diagnostic sensitivity and specificity of host-derived salivary biomarkers in periodontal disease amongst adults: Systematic review / S. Kc, X. Z. Wang, J. E. Gallagher // J Clin Periodontol. - 2020. - Vol. 47 (3). - P. 289-308.</mixed-citation>
     <mixed-citation xml:lang="en">Kc, S., Wang, X. Z., Gallagher, J. E. (2020). Diagnostic sensitivity and specificity of host-derived salivary biomarkers in periodontal disease amongst adults: Systematic review. J Clin Periodontol, 47 (3), 289-308.</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B16">
    <label>16.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Periodontal disease and risk of coronary heart disease: an updated meta-analysis of prospective cohort studies / W. D. Leng, X. T. Zeng, J. S. Kwong [et al.] // Int J Cardiol. - 2015. - Vol. 201. - Р. 469-472.</mixed-citation>
     <mixed-citation xml:lang="en">Leng, W. D., Zeng, X. T., Kwong, J. S. et al. (2015). Periodontal disease and risk of coronary heart disease: an updated meta-analysis of prospective cohort studies. Int J Cardiol, 201, 469-472.</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B17">
    <label>17.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Salivary Profiles as Novel Biomarkers for Oral Diseases / A. I. Lorenzo-Pouso, M. Pérez-Sayáns, S. B. Bravo [et al.] // Dis Markers. - 2018. - Vol. 7.</mixed-citation>
     <mixed-citation xml:lang="en">Lorenzo-Pouso, A. I., Pérez-Sayáns, M., Bravo, S. B. et al. (2018). Salivary Profiles as Novel Biomarkers for Oral Diseases. Dis Markers, 7.</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B18">
    <label>18.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Acute Phase Proteins and Their Role in Periodontitis: A Review / T. Polepalle, S. Moogala [et al.] // J. Clin Diagn Res. - 2015. - Vol. 9 (11). - Р. 1-5.</mixed-citation>
     <mixed-citation xml:lang="en">Polepalle, T., Moogala, S. et al. (2015). Acute Phase Proteins and Their Role in Periodontitis: A Review. J. Clin Diagn Res, 9 (11), 1-5.</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B19">
    <label>19.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Pai, B. S. Correlations between Interleukin-33 and -1α Levels in Gingival Crevicular Fluid and Plasma in Patients with Chronic or Aggressive Periodontitis and Disease-free Subjects / B. S Pai., A. R. Pradeep // Bull Tokyo Dent Coll. - 2019. - Vol. 60 (4). - P. 279-289.</mixed-citation>
     <mixed-citation xml:lang="en">Pai, B. S., Pradeep, A. R. (2019). Correlations between Interleukin-33 and -1α Levels in Gingival Crevicular Fluid and Plasma in Patients with Chronic or Aggressive Periodontitis and Disease-free Subjects. Bull Tokyo Dent Coll, 60 (4), 279-289.</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B20">
    <label>20.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Cytokines and Chemokines in Periodontitis / D. E. Ramadan, N. Hariyani, R. Devijanti, D. Indeswati // European journal of dentistry. - 2020.</mixed-citation>
     <mixed-citation xml:lang="en">Ramadan, D. E., Hariyani, N., Devijanti, R., Indeswati, D. (2020). Cytokines and Chemokines in Periodontitis. European journal of dentistry.</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B21">
    <label>21.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Cytokine-based Predictive Models to Estimate the Probability of Chronic Periodontitis: Development of Diagnostic Nomograms / I. Tomás, N. Arias-Bujanda, M. Alonso-Sampedro [et al.] // Sci Rep. - 2017. - Vol. 7 (1). - P. 11580.</mixed-citation>
     <mixed-citation xml:lang="en">Tomás, I., Arias-Bujanda, N., Alonso-Sampedro, M. et al. (2017). Cytokine-based Predictive Models to Estimate the Probability of Chronic Periodontitis: Development of Diagnostic Nomograms. Sci Rep, 7 (1), 11580.</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B22">
    <label>22.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Increased interleukin-18 in the gingival tissues evokes chronic periodontitis after bacterial infection / K. Yoshinaka, N. Shoji, T. Nishioka, [et al.] // Tohoku J Exp Med. - 2014. - Vol. 232 (3). - P. 215-222.</mixed-citation>
     <mixed-citation xml:lang="en">Yoshinaka, K., Shoji, N., Nishioka, T. et al. (2014). Increased interleukin-18 in the gingival tissues evokes chronic periodontitis after bacterial infection. Tohoku J Exp Med, 232 (3), 215-222.</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B23">
    <label>23.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Salivary biomarker combination prediction model for the diagnosis of periodontitis in a Taiwanese population / Wu. Yun-Chun, N. Lee, T. Yu-Kang [et al.] // J Formos Med Assoc. - 2018. - Vol. 117 (9). - Р. 841-848.</mixed-citation>
     <mixed-citation xml:lang="en">Yun-Chun, Wu., Lee, N., Yu-Kang, T. et al. (2018). Salivary biomarker combination prediction model for the diagnosis of periodontitis in a Taiwanese population. J Formos Med Assoc, 117 (9), 841-848.</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B24">
    <label>24.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Periodontal disease and risk of head and neck cancer: a meta-analysis of observational studies / X. T. Zeng, A. P. Deng [et al.] // PLoS One. - 2013. - Vol. 8(10). - Р. 79017.</mixed-citation>
     <mixed-citation xml:lang="en">Zeng, X. T., Deng, A. P. et al. (2013). Periodontal disease and risk of head and neck cancer: a meta-analysis of observational studies. PLoS One, 8(10).</mixed-citation>
    </citation-alternatives>
   </ref>
   <ref id="B25">
    <label>25.</label>
    <citation-alternatives>
     <mixed-citation xml:lang="ru">Inflammatory cytokine levels in patients withperiodontitis and/or coronary heart disease / H. Zhu, X. Lin, P. Zheng, H. Chen // Int J Clin Exp Pathol. - 2015. - Vol. 8 (2). - P. 2214-2220.</mixed-citation>
     <mixed-citation xml:lang="en">Zhu, H., Lin, X., Zheng, P., Chen, H. (2015). Inflammatory cytokine levels in patients withperiodontitis and/or coronary heart disease. Int J Clin Exp Pathol, 8 (2), 2214-2220.</mixed-citation>
    </citation-alternatives>
   </ref>
  </ref-list>
 </back>
</article>
