ОМ-85: новые молекулярно-клеточные механизмы противовирусного, антибактериального и противовоспалительного действия иммуномодулятора

1. Сильвестров В.П., Караулов А.В. Принципы иммунорегулирующей терапии некоторых заболеваний органов дыхания. Тер. архив. 1982; 4: 3–9. / Sil'vestrov V.P., Karaulov A.V. Printsipy immunoreguliruiushchei terapii nekotorykh zabolevanii organov dykhaniia. Ter. arkhiv. 1982; 4: 3–9. [in Russian]
2. Караулов А.В., Калюжин О.В. Иммунотерапия инфекционных болезней: проблемы и перспективы. Тер. архив. 2013; 11: 100–8. / Karaulov A.V., Kaliuzhin O.V. Immunoterapiia infektsionnykh boleznei: problemy i perspektivy. Ter. arkhiv. 2013; 11: 100–8. [in Russian]
3. Pasquali C, Salami O, Taneja M et al. Enhanced Mucosal Antibody Production and Protection against Respiratory Infections Following an Orally Administered Bacterial. Front Med (Lausanne) 2014; 1: 41. doi: 10.3389/fmed.2014.00041. 
4. Hong Luan, Qian Zhang, Le Wang et al. OM85-BV induced the productions of IL-1 ß, IL-6, and TNF-a via TLR4 and TLR2-mediated ERK1/2/NF-kB pathway in RAW264.7 cells. J Interferon Cytokine Res 2014; 34 (7): 526–36.
5. Navarro S, Cossalter G, Chiavaroli C et. al. The oral administration of bacterial extracts prevents asthma via the recruitment of regulatory T cells to the airways. Mucosal Immunol 2011; 4 (1): 53–65.
6. Караулов А.В. Комментарий к статье А.С.Колбина, А.В.Харчева «Применения иммуностимуляторов при острых инфекциях дыхательных путей у детей». Зарубежный опыт – взгляд с позиций доказательной медицины. Педиатр. фармакология. 2007; 4: 6–7. / Karaulov A.V. Kommentarii k stat'e A.S.Kolbina, A.V.Kharcheva “Primeneniia immunostimuliatorov pri ostrykh infektsiiakh dykhatel'nykh putei u detei”. Zarubezhnyi opyt – vzgliad s pozitsii dokazatel'noi meditsiny. Pediatr. farmakologiia. 2007; 4: 6–7. [in Russian]
7. Feleszko W, Ruszczynski M, Zalewski BM. Non-specific immune stimulation in respiratory tract infections. Separating the wheat from the chaff. Pediatr Res Rev 2014; 15: 200–6.
8. Караулов А.В., Калюжин О.В., Евсегнеева И.В. и др. Эволюция Т-клеточных парадигм при иммунозависимых заболеваниях. Аллергология и иммунология. 2011; 12 (2): 196–8. / Karaulov A.V., Kaliuzhin O.V., Evsegneeva I.V. i dr. Evoliutsiia T-kletochnykh paradigm pri immunozavisimykh zabolevaniiakh. Allergologiia i immunologiia. 2011; 12 (2): 196–8. [in Russian]
9. Huber M, Mossmann H, Bessler WG. Th1-orientated immunological properties of the bacterial extract OM-85-BV. Eur J Med Res 2005; 10 (5): 209–17.
10. Schaad UB, Mütterlein R, Goffin H. Immunostimulation with OM-85 in children with recurrent infections of the upper respiratory tract. Chest 2002; 122: 2042–9.
11. Bessler WG, Huber M, Baier W. Bacterial cell wall components as immunomodulators-II. The bacterial cell wall extract OM-85-BV as unspecific activator, immunogen and adjuvant in mice. Int J Immunopharmac 1997; 19: 551–8.
12. Караулов А.В., Климов Э.В. Клиническая эффективность бактериальных иммуномодуляторов и их влияние на гуморальные и секреторные факторы часто болеющих детей. Педиатрия. 2001; 4: 86–90. / Karaulov A.V., Klimov E.V. Klinicheskaia effektivnost' bakterial'nykh immunomoduliatorov i ikh vliianie na gumoral'nye i sekretornye faktory chasto boleiushchikh detei. Pediatriia. 2001; 4: 86–90. [in Russian]
13. Evans SE, Scott BL, Clement CG et al. Stimulated innate resistance of lung epithelium protects mice broadly against bacteria and fungi. Am J Respir Cell Mol Biol 2010; 42 (1): 40–50.
14. Razi CH, Harmanci K, Abaci A et al. The immunostimulant OM-85 BV prevents wheezing attacks in preschool children. J Allergy Clin Immunol 2010; 126: 763–69.
15. Varghese J. OM-85 in the prevention of asthma in high-risk children. WHO international clinical trials registry platform at http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ACT RN12612000518864 (accessed July 15, 2015).
16. Байракова А.Л., Воропаева Е.А., Афанасьева С.С. и др. Роль и биологическое значение TOLL-LIKERECEPTOR в антиинфекционной резистентности организма. Вестн. РАМН. 2008; 1: 45–54. / Bairakova A.L., Voropaeva E.A., Afanas'eva S.S. 
i dr. Rol' i biologicheskoe znachenie TOLL-LIKERECEPTOR v antiinfektsionnoi rezistentnosti organizma. Vestn. RAMN. 2008; 1: 45–54. [in Russian]
17. Караулов А.В., Несвижский Ю.В., Афанасьев С.С и др. Сравнительный анализ информативно-диагностических свойств показателей иммунореактивности слизистых. ЖМЭИ. 2014; 3: 21–7. / Karaulov A.V., Nesvizhskii Iu.V., Afanas'ev S.S 
i dr. Sravnitel'nyi analiz informativno-diagnosticheskikh svoistv pokazatelei immunoreaktivnosti slizistykh. ZhMEI. 2014; 3: 21–7. [in Russian]
18. Zelle-Rieser C, Ramoner R, Bartsch G, Thurnher M. A clinically approved oral vaccine against pneumotropic bacteria induces the terminal maturation of CD83+ immunostimulatory dendritic cells. Immunol Lett 2001; 76: 63–7.
19. Parola C, Salogni L, Vaira X et al. Selective Activation of Human Dendritic Cells by OM-85 through a NF-kB and MAPK Dependent Pathway. PLoS ONE 2013; 8 (12): e82867. doi:10.1371/journal.pone.0082867
20. Tao Y, Yuan T, Li X et al. Bacterial extract OM-85 BV protects mice against experimental chronic rhinosinusitis. J Clin Exp Pathol 2015; 8 (6): 6800–6. 
21. Alyanakian MA, Grela F, Aumeunier A et al. Transforming growth factor-beta and natural killer T-cells are involved in the protective effect of a bacterial extract on type 1 diabetes. Diabetes 2006; 55: 179–85.
22. Fluckiger AC, Garrone P, Durand I et al. Interleukin 10 (IL-10) upregulates functional high affinity IL-2 receptors on normal and leukemic B lymphocytes. J Exp Med 1993; 178: 1473–81.
23. Rousset F, Garcia E, Defrance T et al. Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci USA 1992; 89: 1890–3.
24. Jego G, Palucka AK, Blanck JP et al. Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Immunity 2003; 19: 225–34.
25. Cerutti A, Chen K, Chorny A. Immunoglobulin responses at the mucosal interface. Ann Rev Immunol 2011; 29: 273–93.
26. Steurer-Stey C, Lagler L, Straub DA et al. Oral purified bacterial extracts in acute respiratory tract infections in childhood: a systematic quantitative review. Eur J Pediatr 2007; 166: 365–76.
27. Del-Rio-Navarro BE, Blandon-Vigil V. Commentary on ‘‘Oral purified bacterial extracts in acute respiratory tract infections in childhood: a systematic review”. Eur J Pediatr 2008; 167: 121–2.
28. Caramori G, Casolari P, Adcock I. Role of transcription factors in the pathogenesis of asthma and COPD. Cell Commun Adhes 2013; 20: 21–40.
29. Mauel J. Stimulation of immunoprotective mechanisms by OM-85 BV. A review of results from in vivo and in vitro studies. Respiration 1994; 61 (Suppl. 1): 8–15.
30. Collet JP, Shapiro P, Ernst P et al. Effects of an immunostimulating agent on acute exacerbations and hospitalizations in patients with chronic obstructive pulmonary disease. The PARI-IS Study Steering Committee and Research Group. Prevention of Acute Respiratory Infection by an Immunostimulant. Am J Respir Crit Care Med 1997; 156: 1719–24.
31. Williams IR. CCR6 and CCL20: partners in intestinal immunity and lymphorganogenesis. Ann N Y AcadSci 2006; 1072: 52–61.
32. Schutyser E, Struyf S, Van Damme J. The CC chemokine CCL20 and its receptor CCR6. Cytokine Growth Factor Rev 2003; 14: 409–26.
33. Yamashita U, Kuroda E. Regulation of macrophage-derived chemokine (MDC, CCL22) production. Crit Rev Immunol 2002; 22: 105–14.
34. Грачев А.Н. Гетерогенность и функциональная пластичность макрофагов второго типа активации. Автореф. дис. …  д-ра биол. наук. М., 1998. / Grachev A.N. Geterogennost' i funktsional'naia plastichnost' makrofagov vtorogo tipa aktivatsii. Avtoref. dis. …  d-ra biol. nauk. M., 1998. [in Russian]
35. Jian Wang, Fengqi Li, Rui Sun et al. Bacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages. Nature Communication 2013; 3 DOI^10.1038/3106
36. van den Bergh MR et al. Associations between pathogens in the upper respiratory tract of young children: interplay between viruses and bacteria. PLoS One 2012; 7 (10): e47711.
37. Караулов А.В., Быков А.С., Быков А.С. Иммунология, микробиология и иммунопатология кожи. М.: Бином, 2012. / Karaulov A.V., Bykov A.S., Bykov A.S. Immunologiia, mikrobiologiia i immunopatologiia kozhi. M.: Binom, 2012. [in Russian]

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1. Sil'vestrov V.P., Karaulov A.V. Printsipy immunoreguliruiushchei terapii nekotorykh zabolevanii organov dykhaniia. Ter. arkhiv. 1982; 4: 3–9. [in Russian]
2. Karaulov A.V., Kaliuzhin O.V. Immunoterapiia infektsionnykh boleznei: problemy i perspektivy. Ter. arkhiv. 2013; 11: 100–8. [in Russian]
3. Pasquali C, Salami O, Taneja M et al. Enhanced Mucosal Antibody Production and Protection against Respiratory Infections Following an Orally Administered Bacterial. Front Med (Lausanne) 2014; 1: 41. doi: 10.3389/fmed.2014.00041. 
4. Hong Luan, Qian Zhang, Le Wang et al. OM85-BV induced the productions of IL-1 ß, IL-6, and TNF-a via TLR4 and TLR2-mediated ERK1/2/NF-kB pathway in RAW264.7 cells. J Interferon Cytokine Res 2014; 34 (7): 526–36.
5. Navarro S, Cossalter G, Chiavaroli C et. al. The oral administration of bacterial extracts prevents asthma via the recruitment of regulatory T cells to the airways. Mucosal Immunol 2011; 4 (1): 53–65.
6. Karaulov A.V. Kommentarii k stat'e A.S.Kolbina, A.V.Kharcheva “Primeneniia immunostimuliatorov pri ostrykh infektsiiakh dykhatel'nykh putei u detei”. Zarubezhnyi opyt – vzgliad s pozitsii dokazatel'noi meditsiny. Pediatr. farmakologiia. 2007; 4: 6–7. [in Russian]
7. Feleszko W, Ruszczynski M, Zalewski BM. Non-specific immune stimulation in respiratory tract infections. Separating the wheat from the chaff. Pediatr Res Rev 2014; 15: 200–6.
8. Karaulov A.V., Kaliuzhin O.V., Evsegneeva I.V. i dr. Evoliutsiia T-kletochnykh paradigm pri immunozavisimykh zabolevaniiakh. Allergologiia i immunologiia. 2011; 12 (2): 196–8. [in Russian]
9. Huber M, Mossmann H, Bessler WG. Th1-orientated immunological properties of the bacterial extract OM-85-BV. Eur J Med Res 2005; 10 (5): 209–17.
10. Schaad UB, Mütterlein R, Goffin H. Immunostimulation with OM-85 in children with recurrent infections of the upper respiratory tract. Chest 2002; 122: 2042–9.
11. Bessler WG, Huber M, Baier W. Bacterial cell wall components as immunomodulators-II. The bacterial cell wall extract OM-85-BV as unspecific activator, immunogen and adjuvant in mice. Int J Immunopharmac 1997; 19: 551–8.
12. Karaulov A.V., Klimov E.V. Klinicheskaia effektivnost' bakterial'nykh immunomoduliatorov i ikh vliianie na gumoral'nye i sekretornye faktory chasto boleiushchikh detei. Pediatriia. 2001; 4: 86–90. [in Russian]
13. Evans SE, Scott BL, Clement CG et al. Stimulated innate resistance of lung epithelium protects mice broadly against bacteria and fungi. Am J Respir Cell Mol Biol 2010; 42 (1): 40–50.
14. Razi CH, Harmanci K, Abaci A et al. The immunostimulant OM-85 BV prevents wheezing attacks in preschool children. J Allergy Clin Immunol 2010; 126: 763–69.
15. Varghese J. OM-85 in the prevention of asthma in high-risk children. WHO international clinical trials registry platform at http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ACT RN12612000518864 (accessed July 15, 2015).
16. Bairakova A.L., Voropaeva E.A., Afanas'eva S.S. 
i dr. Rol' i biologicheskoe znachenie TOLL-LIKERECEPTOR v antiinfektsionnoi rezistentnosti organizma. Vestn. RAMN. 2008; 1: 45–54. [in Russian]
17. Karaulov A.V., Nesvizhskii Iu.V., Afanas'ev S.S 
i dr. Sravnitel'nyi analiz informativno-diagnosticheskikh svoistv pokazatelei immunoreaktivnosti slizistykh. ZhMEI. 2014; 3: 21–7. [in Russian]
18. Zelle-Rieser C, Ramoner R, Bartsch G, Thurnher M. A clinically approved oral vaccine against pneumotropic bacteria induces the terminal maturation of CD83+ immunostimulatory dendritic cells. Immunol Lett 2001; 76: 63–7.
19. Parola C, Salogni L, Vaira X et al. Selective Activation of Human Dendritic Cells by OM-85 through a NF-kB and MAPK Dependent Pathway. PLoS ONE 2013; 8 (12): e82867. doi:10.1371/journal.pone.0082867
20. Tao Y, Yuan T, Li X et al. Bacterial extract OM-85 BV protects mice against experimental chronic rhinosinusitis. J Clin Exp Pathol 2015; 8 (6): 6800–6. 
21. Alyanakian MA, Grela F, Aumeunier A et al. Transforming growth factor-beta and natural killer T-cells are involved in the protective effect of a bacterial extract on type 1 diabetes. Diabetes 2006; 55: 179–85.
22. Fluckiger AC, Garrone P, Durand I et al. Interleukin 10 (IL-10) upregulates functional high affinity IL-2 receptors on normal and leukemic B lymphocytes. J Exp Med 1993; 178: 1473–81.
23. Rousset F, Garcia E, Defrance T et al. Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci USA 1992; 89: 1890–3.
24. Jego G, Palucka AK, Blanck JP et al. Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Immunity 2003; 19: 225–34.
25. Cerutti A, Chen K, Chorny A. Immunoglobulin responses at the mucosal interface. Ann Rev Immunol 2011; 29: 273–93.
26. Steurer-Stey C, Lagler L, Straub DA et al. Oral purified bacterial extracts in acute respiratory tract infections in childhood: a systematic quantitative review. Eur J Pediatr 2007; 166: 365–76.
27. Del-Rio-Navarro BE, Blandon-Vigil V. Commentary on ‘‘Oral purified bacterial extracts in acute respiratory tract infections in childhood: a systematic review”. Eur J Pediatr 2008; 167: 121–2.
28. Caramori G, Casolari P, Adcock I. Role of transcription factors in the pathogenesis of asthma and COPD. Cell Commun Adhes 2013; 20: 21–40.
29. Mauel J. Stimulation of immunoprotective mechanisms by OM-85 BV. A review of results from in vivo and in vitro studies. Respiration 1994; 61 (Suppl. 1): 8–15.
30. Collet JP, Shapiro P, Ernst P et al. Effects of an immunostimulating agent on acute exacerbations and hospitalizations in patients with chronic obstructive pulmonary disease. The PARI-IS Study Steering Committee and Research Group. Prevention of Acute Respiratory Infection by an Immunostimulant. Am J Respir Crit Care Med 1997; 156: 1719–24.
31. Williams IR. CCR6 and CCL20: partners in intestinal immunity and lymphorganogenesis. Ann N Y AcadSci 2006; 1072: 52–61.
32. Schutyser E, Struyf S, Van Damme J. The CC chemokine CCL20 and its receptor CCR6. Cytokine Growth Factor Rev 2003; 14: 409–26.
33. Yamashita U, Kuroda E. Regulation of macrophage-derived chemokine (MDC, CCL22) production. Crit Rev Immunol 2002; 22: 105–14.
34. Grachev A.N. Geterogennost' i funktsional'naia plastichnost' makrofagov vtorogo tipa aktivatsii. Avtoref. dis. …  d-ra biol. nauk. M., 1998. [in Russian]
35. Jian Wang, Fengqi Li, Rui Sun et al. Bacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages. Nature Communication 2013; 3 DOI^10.1038/3106
36. van den Bergh MR et al. Associations between pathogens in the upper respiratory tract of young children: interplay between viruses and bacteria. PLoS One 2012; 7 (10): e47711.
37. Karaulov A.V., Bykov A.S., Bykov A.S. Immunologiia, mikrobiologiia i immunopatologiia kozhi. M.: Binom, 2012. [in Russian]

А.В.Караулов*

ФГБОУ ВО Первый Московский государственный медицинский университет им. И.М.Сеченова Минздрава России. 119991, Россия, Москва, ул. Трубецкая, д. 8, стр. 2
*drkaraulov@mail.ru

________________________________________________

A.V.Karaulov*

I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation. 119991, Russian Federation, Moscow, ul. Trubetskaia, d. 8, str. 2
*drkaraulov@mail.ru