В представленном обзоре проанализированы новые взгляды на проблему воспалительных заболеваний нижнего отдела половых путей, а также данные исследований, посвященных роли местного иммунитета и микрофлоры влагалища в развитии хронических воспалительных заболеваний. Рассмотрена переспектива использования цитокиновых биомаркеров в клинической практике и представлены результаты протеомных исследований цервиковагинальной жидкости в ранней диагностике воспалительных заболеваний.
The present literature review reports on the modern viewpoints on the problem of inflammations of the lower genital tract. The data of investigations of the role of local immunity and vaginal microflora in the development of chronic inflammations were assessed. The use of cytokine biomarkers in clinical practice was discussed and the results of proteomic studies of cervico-vaginal fluid in early diagnosis of inflammations were presented.
1. Arthur T Ollendorff .Cervicitis. Medscape updated, 2012.
2. Ferrero-Miliani L, Nielsen OH, Andersen PS, Girardin SE. 2006 British Society for Immunology.
3. Прилепская В.Н. Патология шейки матки. Медпресс, 2006.
4. Spear GT, Kendrick SR, Chen HY et al. Multiplex Immunoassay of Lower Genital Tract Mucosal Fluid from Women Attending an Urban STD Clinic Shows Broadly Increased IL1b and Lactoferrin. PLoS ONE 6 (5): e19560.doi:10.1371/journal.pone.0019560.
5. Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Ann Rev Immunol 2009; 27: 229–65.
6. Farnaud S, Evans RW. Lactoferrin – a multifunctional protein with antimicrobial properties. Mol Immunol 2003; 40: 395–405.
7. Van der Strate BW, Beljaars L, Molema G et al. Antiviral activities of lactoferrin. Antiviral Res 2001; 52: 225–39.
8. St John E, Mares D, Spear GT. Bacterial vaginosis and host immunity. Curr HIV/AIDS Rep 2007; 4: 22–8.
9. Goldenberg RL, Andrews WW, Guerrant RL et al. The preterm prediction study: cervical lactoferrin concentration, other markers of lower genital tract infection, and preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 2000; 182: 631–5.
10. Agrawal T, Vats V, Wallace PK, Singh A, Salhan S et al. Recruitment of myeloid and plasmacytoid dendritic cells in cervical mucosa during Chlamydia trachomatis infection. Clin Microbiol Infect 2009; 15: 50–9.
11. Sawada M, Otsuki K, Mitsukawa K et al. Cervical inflammatory cytokines and other markers in the cervical mucus of pregnant women with lower genital tract infection. Int J Gynaecol Obstet 2006; 92: 117–21.
12. Ward PP, Paz E, Conneely OM. Multifunctional roles of lactoferrin: a critical overview. Cell Mol Life Sci 2005; 62: 2540–8.
13. Trifonova RT, Bajpai M, Pasicznyk JM et al. Biomarkers of leukocyte traffic and activation in the vaginal mucosa. Biomarkers 2007; 12: 608–22.
14. Ning YM, Wang Y, Lü L et al. Патогенез и клиническое значение IL-8 и TNF-a при цервиците. Zhonghua Yi Xue Za Zhi 2009; 89 (24): 1684–6.
15. Zhang D, Liu ZH, Liao QP et al. Zhonghua Fu Chan Ke Za Zhi 2009; 44 (1): 13–5.
16. Quayle AJ. The innate and early immune response to pathogen challenge in the female genital tract and the pivotal role of epithelial cells. J Reprod Immunol 2002; 57: 61–79.
17. Cole AM. Innate host defense of human vaginal and cervical mucosae. Curr Top Microbiol Immunol 2006; 306: 199–230.
18. Iijima N, Thompson JM, Iwasaki A. Dendritic cells and macrophages in the genitourinary tract. Mucosal Immunol 2008; 1: 451–9.
19. Ochiel DO, Fahey JV, Ghosh M et al. Innate Immunity inthe Female Reproductive Tract: Role of Sex Hormones in RegulatingUterine Epithelial Cell Protection Against Pathogens. Curr Womens Health Rev 2008; 4: 102–17.
20. Eschenbach DA, Thwin SS, Patton DL et al. Influence of the normal menstrual cycleon vaginal tissue, discharge, and microflora. Clin Infect Dis 2000; 30: 901–7.
21. Valore EV, Park CH, Igreti SL, Ganz T. Antimicrobial components of vaginalfluid. Am J Obstet Gynecol 2002; 187: 561–8.
22. Rohan LC, Sassi AB. Vaginal drug delivery systems for HIV prevention. AAPS J 2009; 11: 78–87.
23. Wira CR, Grant-Tschudy KS, Crane-Godreau MA. Epithelial cells in the female reproductive tract: a central role as sentinels of immune protection. Am J Reprod Immunol 2005; 53: 65–76.
24. Klein LL, Jonscher KR, Heerwagen MJ et al. Shotgun proteomic analysis of vaginal fluid from women in late pregnancy. Reprod Sci 2008; 15: 263–73.
25. Thomas PD, Campbell MJ, Kejariwal A et al. PANTHER: a library of protein families and subfamilies indexed by function. Genome Res 2003; 13: 2129–41.
26. Good DM, Thongboonkerd V, Novak J et al. Body fluid proteomics for biomarker discovery: lessons from the past hold the key to success in the future. J Proteome Res 2007; 6: 4549–55.
27. Veenstra TD, Conrads TP, Hood BL et al. Biomarkers: mining the biofluid proteome. Mol Cell Proteomics 2005; 4: 409–18.
28. Hu S, Loo JA, Wong DT. Human body fluid proteome analysis. Proteomics 2006; 6: 6326–53.
29. Schmidt A, Aebersold R. High-accuracy proteome maps of human body fluids. Genome Biol 2006; 7: 242.
30. Schrader M, Selle H. The process chain for peptidomic biomarker discovery. Dis Markers 2006; 22: 27–37.
31. Wira CR, Fahey JV. A new strategy to understand how HIV infects women: identification of a window of vulnerability during the menstrual cycle. AIDS 2008; 22: 1909–17.
32. Shimoya K, Zhang Q, Temma K et al. Secretory leukocyte protease inhibitor levels in cervicovaginal secretion of elderly women. Maturitas 2006; 54: 141–8.
33. Cherpes TL, Marrazzo JM, Cosentino LA et al. Hormonal contraceptive use modulates the local inflammatory response to bacterial vaginosis. Sex Transm Infect 2008; 84: 57–61.
34. Ildgruben A, Sjoberg I, Hammarstrom ML, Backstrom T. Steroid receptor expression in vaginal epithelium of healthy fertile women and influences of hormonal contraceptive usage. Contraception 2005; 72: 383–92.
35. Ildgruben AK, Sjoberg IM, Hammarstrom ML. Influence of hormonal contraceptives on the immune cells and thickness of human vaginal epithelium. Obstet Gynecol 2003; 102: 571–82.
36. Di Quinzio MK, Georgiou HM, Holdsworth-Carson SJ et al. Proteomic analysis of human cervicovaginal fluid displays differential protein expression in association with labor onset at term. J Proteome Res 2008; 7: 1916–21.
37. St John E, Mares D, Spear GT. Bacterial vaginosis and host immunity. Curr HIV/AIDS Rep 2007; 4: 22–8.
38. Balu RB, Savitz DA, Ananth CV et al. Bacterial vaginosis, vaginal fluid neutrophil defensins, and preterm birth. Obstet Gynecol 2003; 101: 862–8.
39. Novak RM, Donoval BA, Graham PJ et al. Cervicovaginal levels of lactoferrin, secretoryleukocyte protease inhibitor, and RANTES and the effects of coexisting vaginoses in human immunodeficiency virus (HIV)-seronegative women with a high risk of heterosexual acquisition of HIV infection. Clin Vaccine Immunol 2007; 14: 1102–7.
40. Valore EV, Wiley DJ, Ganz T. Reversible deficiency of antimicrobial polypeptides in bacterial vaginosis. Infect Immun 2006; 74: 5693–702.
41. Wiesenfeld HC, Heine RP, Krohn MA et al. Association between elevated neutrophil defensin levels and endometritis. J Infect Dis 2002; 186: 792–7.
42. Xu J, Holzman CB, Arvidson CG et al. Midpregnancy vaginal fluid defensins, bacterial vaginosis, and risk of preterm delivery. Obstet Gynecol 2008; 112: 524–31.
43. Spear GT, St JE, Zariffard MR. Bacterial vaginosis and human immunodeficiency virus infection. AIDS Res Ther 2007; 4: 25.
44. Heng YJ, Di Quinzio MK, Permezel M et al. Interleukin-1 receptor antagonist in human cervicovaginal fluid in term pregnancy and labor. Am J Obstet Gynecol 2008; 199: 656–7.
45. Heng YJ, Di Quinzio MK, Permezel M et al. Temporal proteomic analysis of human cervicovaginal fluid withimpending term labor. J Proteome Res 2010; 9: 1344–50.
46. Goffinet F, Kayem G, Maillard F et al. Detection of interleukin 6 mRNA by RT-PCR in vaginal secretions: association with preterm delivery and neonatal infection in women with preterm labour and intact membranes. Eur J Obstet Gynecol Reprod Biol 2005; 123 (2): 167–73.
47. Yasodhara P, Raghunath M, Sreeramulu D et al. Local immunity in Indian women with bacterial vaginosis. J Reprod Immunol 2006; 70 (1–2): 133–41.
48. Meng W, Du R, Wang Y et al. Human b-Defensin Messenger RNA is Overexpressed in the Cervical Epithelia of Patients With Nongonococcal Cervicitis. J Low Genit Tract Dis 2013.
49. Paavonen J, Critchlow CW, DeRouen T et al. Etiology of cervicalinflammation. Am J Obstet Gynecol 1986; 154: 556–64.
50. Jane R Schwebke, Heidi L. Weiss Interrelationships of Bacterial Vaginosis and Cervical Inflammation Sexually Transmitted Diseases Jan 200259-64.
51. Сухих Г.Т., Трофимов Д.Ю., Бурменская О.В. и др. Профиль экспрессии мРНК генов цитокинов в вагинальных мазках женщин репродуктивного возраста при неспецифическом вагините и бактериальном вагинозе. Акуш. и гинекол. 2011; 7–2: 33–8.
52. Костава М.Н., Байрамова Г.Р. Оценка эффективности и приемлемости комбинированной терапии неспецифического вагинита и цервицита. Гинекология. 2011; 1: 4–7.
53. Чигринец О.В. Этиологические и патогенетические аспекты, оптимизация диагностики и терапии хронических цервицитов. Автореф. Челябинск, 2004.
54. Кира Е.Ф. Бактериальный вагиноз. СПб.: Нева-люкс, 2001.
55. Липова Е.В., Хрзаян Р.С. Эффективность монотерапии бактериального вагиноза и урогенитального кандидоза тержинаном – комбинированным местнодействующим препаратом. Рос. вестн. акушера-гинеколога. 2006; 6 (5): 66–8.
56. Каратюк Т.И. Опыт применения комбинированного препарата, содержащего неомицин, нистатин, преднизолон, тернидазол, при лечении воспалительных заболеваний нижнего отдела гениталий у женщин. Рос. вестн. акушера-гинеколога. 2012; 6: 76–80.
57. Прилепская В.Н. Вагинальные инфекции и локальные препараты комплексного действия. В чем причина успеха? Гинекология. 2011; 13 (6).
________________________________________________
1. Arthur T Ollendorff .Cervicitis. Medscape updated, 2012.
2. Ferrero-Miliani L, Nielsen OH, Andersen PS, Girardin SE. 2006 British Society for Immunology.
3. Прилепская В.Н. Патология шейки матки. Медпресс, 2006.
4. Spear GT, Kendrick SR, Chen HY et al. Multiplex Immunoassay of Lower Genital Tract Mucosal Fluid from Women Attending an Urban STD Clinic Shows Broadly Increased IL1b and Lactoferrin. PLoS ONE 6 (5): e19560.doi:10.1371/journal.pone.0019560.
5. Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Ann Rev Immunol 2009; 27: 229–65.
6. Farnaud S, Evans RW. Lactoferrin – a multifunctional protein with antimicrobial properties. Mol Immunol 2003; 40: 395–405.
7. Van der Strate BW, Beljaars L, Molema G et al. Antiviral activities of lactoferrin. Antiviral Res 2001; 52: 225–39.
8. St John E, Mares D, Spear GT. Bacterial vaginosis and host immunity. Curr HIV/AIDS Rep 2007; 4: 22–8.
9. Goldenberg RL, Andrews WW, Guerrant RL et al. The preterm prediction study: cervical lactoferrin concentration, other markers of lower genital tract infection, and preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 2000; 182: 631–5.
10. Agrawal T, Vats V, Wallace PK, Singh A, Salhan S et al. Recruitment of myeloid and plasmacytoid dendritic cells in cervical mucosa during Chlamydia trachomatis infection. Clin Microbiol Infect 2009; 15: 50–9.
11. Sawada M, Otsuki K, Mitsukawa K et al. Cervical inflammatory cytokines and other markers in the cervical mucus of pregnant women with lower genital tract infection. Int J Gynaecol Obstet 2006; 92: 117–21.
12. Ward PP, Paz E, Conneely OM. Multifunctional roles of lactoferrin: a critical overview. Cell Mol Life Sci 2005; 62: 2540–8.
13. Trifonova RT, Bajpai M, Pasicznyk JM et al. Biomarkers of leukocyte traffic and activation in the vaginal mucosa. Biomarkers 2007; 12: 608–22.
14. Ning YM, Wang Y, Lü L et al. Патогенез и клиническое значение IL-8 и TNF-a при цервиците. Zhonghua Yi Xue Za Zhi 2009; 89 (24): 1684–6.
15. Zhang D, Liu ZH, Liao QP et al. Zhonghua Fu Chan Ke Za Zhi 2009; 44 (1): 13–5.
16. Quayle AJ. The innate and early immune response to pathogen challenge in the female genital tract and the pivotal role of epithelial cells. J Reprod Immunol 2002; 57: 61–79.
17. Cole AM. Innate host defense of human vaginal and cervical mucosae. Curr Top Microbiol Immunol 2006; 306: 199–230.
18. Iijima N, Thompson JM, Iwasaki A. Dendritic cells and macrophages in the genitourinary tract. Mucosal Immunol 2008; 1: 451–9.
19. Ochiel DO, Fahey JV, Ghosh M et al. Innate Immunity inthe Female Reproductive Tract: Role of Sex Hormones in RegulatingUterine Epithelial Cell Protection Against Pathogens. Curr Womens Health Rev 2008; 4: 102–17.
20. Eschenbach DA, Thwin SS, Patton DL et al. Influence of the normal menstrual cycleon vaginal tissue, discharge, and microflora. Clin Infect Dis 2000; 30: 901–7.
21. Valore EV, Park CH, Igreti SL, Ganz T. Antimicrobial components of vaginalfluid. Am J Obstet Gynecol 2002; 187: 561–8.
22. Rohan LC, Sassi AB. Vaginal drug delivery systems for HIV prevention. AAPS J 2009; 11: 78–87.
23. Wira CR, Grant-Tschudy KS, Crane-Godreau MA. Epithelial cells in the female reproductive tract: a central role as sentinels of immune protection. Am J Reprod Immunol 2005; 53: 65–76.
24. Klein LL, Jonscher KR, Heerwagen MJ et al. Shotgun proteomic analysis of vaginal fluid from women in late pregnancy. Reprod Sci 2008; 15: 263–73.
25. Thomas PD, Campbell MJ, Kejariwal A et al. PANTHER: a library of protein families and subfamilies indexed by function. Genome Res 2003; 13: 2129–41.
26. Good DM, Thongboonkerd V, Novak J et al. Body fluid proteomics for biomarker discovery: lessons from the past hold the key to success in the future. J Proteome Res 2007; 6: 4549–55.
27. Veenstra TD, Conrads TP, Hood BL et al. Biomarkers: mining the biofluid proteome. Mol Cell Proteomics 2005; 4: 409–18.
28. Hu S, Loo JA, Wong DT. Human body fluid proteome analysis. Proteomics 2006; 6: 6326–53.
29. Schmidt A, Aebersold R. High-accuracy proteome maps of human body fluids. Genome Biol 2006; 7: 242.
30. Schrader M, Selle H. The process chain for peptidomic biomarker discovery. Dis Markers 2006; 22: 27–37.
31. Wira CR, Fahey JV. A new strategy to understand how HIV infects women: identification of a window of vulnerability during the menstrual cycle. AIDS 2008; 22: 1909–17.
32. Shimoya K, Zhang Q, Temma K et al. Secretory leukocyte protease inhibitor levels in cervicovaginal secretion of elderly women. Maturitas 2006; 54: 141–8.
33. Cherpes TL, Marrazzo JM, Cosentino LA et al. Hormonal contraceptive use modulates the local inflammatory response to bacterial vaginosis. Sex Transm Infect 2008; 84: 57–61.
34. Ildgruben A, Sjoberg I, Hammarstrom ML, Backstrom T. Steroid receptor expression in vaginal epithelium of healthy fertile women and influences of hormonal contraceptive usage. Contraception 2005; 72: 383–92.
35. Ildgruben AK, Sjoberg IM, Hammarstrom ML. Influence of hormonal contraceptives on the immune cells and thickness of human vaginal epithelium. Obstet Gynecol 2003; 102: 571–82.
36. Di Quinzio MK, Georgiou HM, Holdsworth-Carson SJ et al. Proteomic analysis of human cervicovaginal fluid displays differential protein expression in association with labor onset at term. J Proteome Res 2008; 7: 1916–21.
37. St John E, Mares D, Spear GT. Bacterial vaginosis and host immunity. Curr HIV/AIDS Rep 2007; 4: 22–8.
38. Balu RB, Savitz DA, Ananth CV et al. Bacterial vaginosis, vaginal fluid neutrophil defensins, and preterm birth. Obstet Gynecol 2003; 101: 862–8.
39. Novak RM, Donoval BA, Graham PJ et al. Cervicovaginal levels of lactoferrin, secretoryleukocyte protease inhibitor, and RANTES and the effects of coexisting vaginoses in human immunodeficiency virus (HIV)-seronegative women with a high risk of heterosexual acquisition of HIV infection. Clin Vaccine Immunol 2007; 14: 1102–7.
40. Valore EV, Wiley DJ, Ganz T. Reversible deficiency of antimicrobial polypeptides in bacterial vaginosis. Infect Immun 2006; 74: 5693–702.
41. Wiesenfeld HC, Heine RP, Krohn MA et al. Association between elevated neutrophil defensin levels and endometritis. J Infect Dis 2002; 186: 792–7.
42. Xu J, Holzman CB, Arvidson CG et al. Midpregnancy vaginal fluid defensins, bacterial vaginosis, and risk of preterm delivery. Obstet Gynecol 2008; 112: 524–31.
43. Spear GT, St JE, Zariffard MR. Bacterial vaginosis and human immunodeficiency virus infection. AIDS Res Ther 2007; 4: 25.
44. Heng YJ, Di Quinzio MK, Permezel M et al. Interleukin-1 receptor antagonist in human cervicovaginal fluid in term pregnancy and labor. Am J Obstet Gynecol 2008; 199: 656–7.
45. Heng YJ, Di Quinzio MK, Permezel M et al. Temporal proteomic analysis of human cervicovaginal fluid withimpending term labor. J Proteome Res 2010; 9: 1344–50.
46. Goffinet F, Kayem G, Maillard F et al. Detection of interleukin 6 mRNA by RT-PCR in vaginal secretions: association with preterm delivery and neonatal infection in women with preterm labour and intact membranes. Eur J Obstet Gynecol Reprod Biol 2005; 123 (2): 167–73.
47. Yasodhara P, Raghunath M, Sreeramulu D et al. Local immunity in Indian women with bacterial vaginosis. J Reprod Immunol 2006; 70 (1–2): 133–41.
48. Meng W, Du R, Wang Y et al. Human b-Defensin Messenger RNA is Overexpressed in the Cervical Epithelia of Patients With Nongonococcal Cervicitis. J Low Genit Tract Dis 2013.
49. Paavonen J, Critchlow CW, DeRouen T et al. Etiology of cervicalinflammation. Am J Obstet Gynecol 1986; 154: 556–64.
50. Jane R Schwebke, Heidi L. Weiss Interrelationships of Bacterial Vaginosis and Cervical Inflammation Sexually Transmitted Diseases Jan 200259-64.
51. Сухих Г.Т., Трофимов Д.Ю., Бурменская О.В. и др. Профиль экспрессии мРНК генов цитокинов в вагинальных мазках женщин репродуктивного возраста при неспецифическом вагините и бактериальном вагинозе. Акуш. и гинекол. 2011; 7–2: 33–8.
52. Костава М.Н., Байрамова Г.Р. Оценка эффективности и приемлемости комбинированной терапии неспецифического вагинита и цервицита. Гинекология. 2011; 1: 4–7.
53. Чигринец О.В. Этиологические и патогенетические аспекты, оптимизация диагностики и терапии хронических цервицитов. Автореф. Челябинск, 2004.
54. Кира Е.Ф. Бактериальный вагиноз. СПб.: Нева-люкс, 2001.
55. Липова Е.В., Хрзаян Р.С. Эффективность монотерапии бактериального вагиноза и урогенитального кандидоза тержинаном – комбинированным местнодействующим препаратом. Рос. вестн. акушера-гинеколога. 2006; 6 (5): 66–8.
56. Каратюк Т.И. Опыт применения комбинированного препарата, содержащего неомицин, нистатин, преднизолон, тернидазол, при лечении воспалительных заболеваний нижнего отдела гениталий у женщин. Рос. вестн. акушера-гинеколога. 2012; 6: 76–80.
57. Прилепская В.Н. Вагинальные инфекции и локальные препараты комплексного действия. В чем причина успеха? Гинекология. 2011; 13 (6).