GynecologyGynecology2079-56962079-5831Consilium Medicum28225Research ArticleImmunologic and molecular-biological markers associated with chronic cervititisPrilepskayaV NVPrilepskaya@mail.ruNazarovaN Mgrab2@yandex.ruNovikovaE Ptaukita.matsuda@gmail.comTrofimovD Yud.trofimov@dna-tech.ruBurmenskayaO Vo_bourmenskaya@oparina4.ruBeznoschenkoO S-15062013153465109042020Copyright © 2013, Consilium Medicum2013The 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.cervititiscytokinescervical fluidцервицитцитокиныцервиковагинальная жидкость[Arthur T Ollendorff.Cervicitis. Medscape updated, 2012.][Ferrero-Miliani L, Nielsen O.H, Andersen P.S, Girardin S.E. 2006 British Society for Immunology.][Прилепская В.Н. Патология шейки матки. Медпресс, 2006.][Spear G.T, Kendrick S.R, Chen H.Y 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.][Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Ann Rev Immunol 2009; 27: 229–65.][Farnaud S, Evans R.W. Lactoferrin – a multifunctional protein with antimicrobial properties. Mol Immunol 2003; 40: 395–405.][Van der Strate B.W, Beljaars L, Molema G et al. Antiviral activities of lactoferrin. Antiviral Res 2001; 52: 225–39.][St John E, Mares D, Spear G.T. Bacterial vaginosis and host immunity. Curr HIV/AIDS Rep 2007; 4: 22–8.][Goldenberg R.L, Andrews W.W, Guerrant R.L 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.][Agrawal T, Vats V, Wallace P.K, 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.][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.][Ward P.P, Paz E, Conneely O.M. Multifunctional roles of lactoferrin: a critical overview. Cell Mol Life Sci 2005; 62: 2540–8.][Trifonova R.T, Bajpai M, Pasicznyk J.M et al. Biomarkers of leukocyte traffic and activation in the vaginal mucosa. Biomarkers 2007; 12: 608–22.][Ning Y.M, 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.][Zhang D, Liu Z.H, Liao Q.P et al. Zhonghua Fu Chan Ke Za Zhi 2009; 44 (1): 13–5.][Quayle A.J. 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.][Cole A.M. Innate host defense of human vaginal and cervical mucosae. Curr Top Microbiol Immunol 2006; 306: 199–230.][Iijima N, Thompson J.M, Iwasaki A. Dendritic cells and macrophages in the genitourinary tract. Mucosal Immunol 2008; 1: 451–9.][Ochiel D.O, Fahey J.V, Ghosh M et al. Innate Immunity inthe Female Reproductive Tract: Role of Sex Hormones in Regulating Uterine Epithelial Cell Protection Against Pathogens. Curr Womens Health Rev 2008; 4: 102–17.][Eschenbach D.A, Thwin S.S, Patton D.L et al. Influence of the normal menstrual cycleon vaginal tissue, discharge, and microflora. Clin Infect Dis 2000; 30: 901–7.][Valore E.V, Park C.H, Igreti S.L, Ganz T. Antimicrobial components of vaginalfluid. Am J Obstet Gynecol 2002; 187: 561–8.][Rohan L.C, Sassi A.B. Vaginal drug delivery systems for HIV prevention. AAPS J 2009; 11: 78–87.][Wira C.R, Grant-Tschudy K.S, Crane-Godreau M.A. Epithelial cells in the female reproductive tract: a central role as sentinels of immune protection. Am J Reprod Immunol 2005; 53: 65–76.][Klein L.L, Jonscher K.R, Heerwagen M.J et al. Shotgun proteomic analysis of vaginal fluid from women in late pregnancy. Reprod Sci 2008; 15: 263–73.][Thomas P.D, Campbell M.J, Kejariwal A et al. PANTHER: a library of protein families and subfamilies indexed by function. Genome Res 2003; 13: 2129–41.][Good D.M, 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.][Veenstra T.D, Conrads T.P, Hood B.L et al. Biomarkers: mining the biofluid proteome. Mol Cell Proteomics 2005; 4: 409–18.][Hu S, Loo J.A, Wong D.T. Human body fluid proteome analysis. Proteomics 2006; 6: 6326–53.][Schmidt A, Aebersold R. High - accuracy proteome maps of human body fluids. Genome Biol 2006; 7: 242.][Schrader M, Selle H. The process chain for peptidomic biomarker discovery. Dis Markers 2006; 22: 27–37.][Wira C.R, Fahey J.V. A new strategy to understand how HIV infects women: identification of a window of vulnerability during the menstrual cycle. AIDS 2008; 22: 1909–17.][Shimoya K, Zhang Q, Temma K et al. Secretory leukocyte protease inhibitor levels in cervicovaginal secretion of elderly women. Maturitas 2006; 54: 141–8.][Cherpes T.L, Marrazzo J.M, Cosentino L.A et al. Hormonal contraceptive use modulates the local inflammatory response to bacterial vaginosis. Sex Transm Infect 2008; 84: 57–61.][Ildgruben A, Sjoberg I, Hammarstrom M.L, Backstrom T. Steroid receptor expression in vaginal epithelium of healthy fertile women and influences of hormonal contraceptive usage. Contraception 2005; 72: 383–92.][Ildgruben A.K, Sjoberg I.M, Hammarstrom M.L. Influence of hormonal contraceptives on the immune cells and thickness of human vaginal epithelium. Obstet Gynecol 2003; 102: 571–82.][Di Quinzio M.K, Georgiou H.M, Holdsworth-Carson S.J 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.][St John E, Mares D, Spear G.T. Bacterial vaginosis and host immunity. Curr HIV/AIDS Rep 2007; 4: 22–8.][Balu R.B, Savitz D.A, Ananth C.V et al. Bacterial vaginosis, vaginal fluid neutrophil defensins, and preterm birth. Obstet Gynecol 2003; 101: 862–8.][Novak R.M, Donoval B.A, Graham P.J 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.][Valore E.V, Wiley D.J, Ganz T. Reversible deficiency of antimicrobial polypeptides in bacterial vaginosis. Infect Immun 2006; 74: 5693–702.][Wiesenfeld H.C, Heine R.P, Krohn M.A et al. Association between elevated neutrophil defensin levels and endometritis. J Infect Dis 2002; 186: 792–7.][Xu J, Holzman C.B, Arvidson C.G et al. Midpregnancy vaginal fluid defensins, bacterial vaginosis, and risk of preterm delivery. Obstet Gynecol 2008; 112: 524–31.][Spear G.T, St J.E, Zariffard M.R. Bacterial vaginosis and human immunodeficiency virus infection. AIDS Res Ther 2007; 4: 25.][Heng Y.J, Di Quinzio M.K, 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.][Heng Y.J, Di Quinzio M.K, Permezel M et al. Temporal proteomic analysis of human cervicovaginal fluid withimpending term labor. J Proteome Res 2010; 9: 1344–50.][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.][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.][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.][Paavonen J, Critchlow C.W, De Rouen T et al. Etiology of cervicalinflammation. Am J Obstet Gynecol 1986; 154: 556–64.][Jane R Schwebke, Heidi L. Weiss Interrelationships of Bacterial Vaginosis and Cervical Inflammation Sexually Transmitted Diseases Jan 200259-64.][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.][Костава М.Н., Байрамова Г.Р. Оценка эффективности и приемлемости комбинированной терапии неспецифического вагинита и цервицита. Гинекология. 2011; 1: 4–7.][Чигринец О.В. Этиологические и патогенетические аспекты, оптимизация диагностики и терапии хронических цервицитов. Автореф. Челябинск, 2004.][Кира Е.Ф. Бактериальный вагиноз. Спб.: Нева - люкс, 2001.][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.][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.][Прилепская В.Н. Вагинальные инфекции и локальные препараты комплексного действия. В чем причина успеха? Гинекология. 2011; 13 (6).]