CHANGES IN SERUM LEVELS OF PRO- AND ANTI-INFLAMMATORY CYTOKINES IN WOMEN WITH PAPILLOMAVIRUS INFECTION BEFORE AND AFTER THERAPY

T.A. Nevezhkina¹, E.V. Markelova¹, S.V. Knysh¹, M.S. Tulupova², L.S. Matyshkina¹

DOI: 10.22138/2500-0918-2022-19-3-241-253

 

¹ Pacific state medical university, Vladivostok, Russian Federation;
² Paracelsus LLC, Vladivostok, Russian Federation

Abstract. The group of papillomaviruses is one of the most common viral infections among sexually transmitted diseases in the young population. A long, sluggish inflammatory process significantly worsens adequate pre-gravidar preparation. Along with papillomavirus infection, herpesvirus and chlamydia infections are the most frequent associations. Many authors believe that PVI reveals dysregulation of pro- and anti-inflammatory cytokines in the blood serum. Currently, there are no uniform standards for the management and treatment of women with papillomavirus infection without pronounced clinical manifestations to prevent morphofunctional disorders of the genitourinary system leading to reproductive disorders. But most authors believe that the use of antiviral and immunomodulatory drugs is the main method of therapy against the proliferation of pathogens in the body. The aim of the study was to compare changes in the levels of IL-17, IL-12 p70, IL-12 p40, IL-13 and TFR-β1 in the blood serum of women with papillomavirus infection before and after therapy with Inosine pranobex (IP) and Solanum tuberosum (ST). Materials and methods: a survey of 137 patients with papillomavirus infection treated with drugs with the active substance Inosine pranobex and Solanum tuberosum was conducted. The levels of IL-17, IL-12 p70, IL-12 p40, IL-13, and TFR-β1 in blood serum were determined using specific reagents from R&D Diagnostics Inc. (USA). Results. Changes in pro- and anti-inflammatory cytokines before therapy: decrease — IL-12 p70, p40, increase — IL-13, IL-17 and TFR-β1. After therapy, the following changes were revealed in the group of patients exclusively with PVI infection when using the drug of synthetic origin IP: the levels of IL-12 p70, IL-12 p40 and a decrease in IL-13 and TFR-β1 increased, while with ST therapy: an increase in IL-12 p70, IL-12 p40 and a decrease in IL-13 and TFR-β1. With IP therapy, patients with HPV+HVI registered an increase in IL-12 p70, IL-12 p40 and a decrease in IL-13, while TFR-β1 did not change, and with ST therapy, IL-12 p70, IL-12 p40 also increased and IL-13 decreased, TFR-β1 remained unchanged. In the group of women with HPV+chlamydia infection, an increase in IL-12 p70, IL-12 p40 and a decrease in IL-13 and TFR-β1 with IP therapy, and an increase in IL-12 p70, IL-12 p40 and a decrease in IL-13 and TFR-β1 with ST therapy were shown. In all groups of patients, IL-17 remained high after therapy without a statistically significant difference between the subgroups. In the groups of patients treated with IP, a predominant normalization of the degree of immune disorders was recorded.

Keywords: human papillomavirus, cytokines, antiviral therapy

There is no conflict of interest.
Contact details of the corresponding author:
Tatiana A. Nevezhkina
tanya.ru9292@mail.ru
Received 14.05.2021
For citation:
Nevezhkina T.A., Markelova E.V., Knysh S.V., Tulupova M.S., Matyshkina L.S. Changes in serum levels of pro- and anti-inflammatory cytokines in women with papillomavirus infection before and after therapy. Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2022, Vol. 19, no. 3, pp. 241–253. DOI: 10.22138/2500-0918-2022-19-3-241-253 (In Russ)

REFERENCES
1. Vaccination of diseases caused by the human papillomavirus: positions of evidence-based medicine. Review of clinical recommendations. A.A. Baranov, L.S. Namazova-Baranova, V.K. Tatochenko, E.A. Vishneva [et al.] Issues of modern pediatrics. – 2017. – Vol. 16, No. 2. – pp. 107-117. DOI: 10.31631/2073-3046-2019-18-6-98-108 (in Russ)
2. Varlamov, E. E. The significance of cytokines in the pathogenesis of atopic dermatitis / E. E. Varlamov, E. E. Pampura, A. N. Sukhorukov. Russian Bulletin of Perinatology and Pediatrics. — 2018. – Vol. 63, No. 1. – pp. 28-33. DOI: 10.21508/1027-4065-2018-63-1-28-33 (in Russ)
3. Dyudyun, A. D. Herpesvirus infection. Clinical and immunological features: clinical lecture. A.D. Dyudyun, N.N. Polion, A.E. Nagorny. Dermatovenerology. Cosmetology. Sexopathology. — 2015. – No. 3-4. – pp. 119-142. (in Russ)
4. Zemskov, A.M. Combined immunocorrection: monograph. A.M. Zemskov, A.V. Karaulov, V. M. Zemskov; Department of Physiology of the Russian Academy of Sciences, Acad. natural sciences, Biomedical Research Institute. and therapy. – Moscow: Nauka, 1994. – 260 p. – ISBN 5-02-004177-7. (un Russ)
5. Ignatovich, T. V. Immunopathogenesis of fibrosis. T. V. Ignatovich, M. M. Zafranskaya. Immunopathology, allergology, infectology. – 2019. – No. 1. – pp. 6-17. DOI: 10.14427/jipai.2019.1.6 (in Russ)
6. Ivleva, N. F. Comparative effectiveness of various methods of treatment of cervical diseases. N. F. Ivlieva, G. V. Chizhkova, N. E. Permina. Far Eastern Medical Journal. – 2013. – No. 3. – pp. 46-49. DOI: 10.20953/1817-7646-2018-5-62-67 (in Russ)
7. Kizey I. N. Modern ideas about the etiopathogenesis of papillomavirus infection. I. N. Kizey, G. A. Naumchik, N. B. Sereda. Pacific Medical Journal. – 2010. – No. 3. – pp.10-15. DOI: 10.17816/JOWD6253-14 (in Russ)
8. Clinical immunology: textbook for students of medical universities. edited by A.V. Karaulov. – Moscow: MIA, 1999. – 604 p. (in Russ)
9. Kustova, M. A. Papillomavirus and concomitant infection of the genitals in pregnant women with HIV-negative and HIV-positive status. M. A. Kustova. Problems of health and ecology. — 2012. – No. 2. – pp. 77-84. DOI: 10.17816/JOWD48672 (in Russ)
10. Melnikov, V. L. Autoimmune diseases: textbook. V. L. Melnikov, N. N. Mitrofanova, L. V. Melnikov. – Penza: Publishing House of PSU, 2015. – 68 p. – ISBN 978-5-906831-39-2 (in Russ)
11. Microbial pathogens in urogenital infection of pregnant women. A.V. Karaulov, M. S. Afanasyev, Yu. V. Nesvizh, S. S. Afanasyev [et al.] Journal of Microbiology, Epidemiology and Immunobiology. – 2019. – No. 6. – pp. 13-20. DOI: 10.36233/0372-9311-2019-6-13-20 (in Russ)
12. Noninvasive methods of treatment of patients with HPV infection and cervical intraepithelial neoplasia: a systematic review and meta-analysis. I. I. Baranov, N. V. Zarochentseva, V.V. Malinovskaya, E.N. Vyzhlova. Obstetrics and Gynecology: News. Opinions. Training. – 2021. – Vol. 9, No. 1. – pp. 31-43. DOI: 10.33029/2303-9698-2021-9-1-31-43 (in Russ)
13. Ruzhentsova, T. A. Results of the use of interferon α-2B in combination with vitamins E and C in the treatment of urogenital infections in pregnant women. T. A. Ruzhentsova, D. A. Khavkina, E. K. Shushakova. Attending physician. – 2021. – No. 1. – pp. 31-36. DOI: 10.26295/ 0S.2021.70.35.007 (in Russ)
14. Tubal infertility as a factor in reducing ovarian reserve: psychoemotional and social aspects. V. N. Nikolenko, N. A. Rizaeva, M. V. Oganesyan, M. S. Golyshkina [et al.] Crimean Journal of Experimental and Clinical Medicine. – 2020. – Vol.10, No. 3. – pp. 110-111. (in Russ)
15. Khaitov, R. M. Immunology: Atlas. R. M. Khaitov, F. Yu. Garib. – 2nd ed., updated. – Moscow: GEODTAR-Media, 2020. – 416 p. – ISBN 978-5-9704-5525-8. DOI: 10.33029/9704-5525-8 (in Russ)
16. Shulzhenko, A. E. Persistent papillomavirus infection: cytokine imbalance and approaches to therapy. Effective pharmacotherapy. A. E. Shulzhenko, I. N. Zuikova. Obstetrics and gynecology. — 2013. – No. 2. – pp. 54-60. (in Russ)
17. Shulzhenko, A. E. Antiviral immunity of the reproductive tract: from studying the system to correcting work. A. E. Shulzhenko, R. V. Shchubelko, I. N. Zuikova. Russian Medical Journal. – 2019. – No.12. – pp. 14-19. (in Russ)
18. Autoimmunity, IBD, and cancer Regulation of IL-12p40 by HIF controls Th1/Th17 responses to prevent mucosal inflammation. E Marks, C. Naudin,G. Nolan, B. J. Goggins [et al.] Mucosal Immunology. – 2017. – Vol. 10. – pp. 1224–1236 DOI: 10.1038/mi.2016.135
19. Bull seminal plasma stimulates in vitro production of TGF-β, IL-6 and IL-8 from bovine endometrial epithelial cells, depending on dose and bull fertility. T. Nongbuaab, Y. Guoa, T. Ntallarisa, M. Rubérc [et. al.] Journal of Reproductive Immunology. – 2020. – Vol. 142. – P. 103-179. DOI: 10.1016/j.jri.2020.103179
20. Cervical Cytokines Associated with Chlamydia trachomatis Susceptibility and Protection. T. B. Poston, De’Ashia E. Lee, T. Darville, W. Zhong [et al.] The Journal of Infectious Diseases. – 2019. – Vol.220(2). – P. 330–339. DOI: 10.1093/infdis/jiz087
21. Chlamydia trachomatis prevalence and chlamydial/HPV co-infection among HPV-unvaccinated young Italian females with normal cytology. D. Panatto, D. Amicizia, S.Bianchi, E. Rosanna Frati [et. al.] Hum Vaccin Immunother. – 2015. – Vol. 11 (1). – P.270-276. DOI: 10.4161/hv.36163
22. Correlation between matrix metalloproteinase expression and activation of the focal adhesion kinase signaling pathway in herpes stromal keratitis. T. Cao, Y. Xing, Y. Yang, H. Mei. Experimental and Therapeutic Medicine. – 2014. – Vol. 7, Is. 1. – pp. 280–286. DOI: 10.3892/etm.2013.1407
23. Discovery of blood transcriptional endotypes in women with pelvic inflammatory disease. X. Zheng, C.M. O’Connell, W. Zhong [et al.] The Journal of Immunology. – 2018. – № 200. – P. 2941–2956. DOI: 10.4049/jimmunol.1701658
24. HPV and Chlamydia trachomatis co-detection in young asymptomatic women from high incidence area for cervical cancer. S. Bellaminutti, S. Seraceni, F. De Seta, T. Gheit, M. Tommasino, M. Comar. J Med Virol. – 2014. – Vol. 86(11). – pp. 1920-1925. DOI: 10.1002/jmv.24041
25. Human Papilloma Virus (HPV) and Fertilization: A Mini Review. K. Zacharis, Ch. I. Messini, G. Anifandis, G. Koukoulis [et.al.] Medicina (Kaunas). – 2018. – Vol. 54, Is. 4. – pp. 50. DOI: 10.3390/medicina54040050
26. Shulzhenko, A. L. Genital herpes: clinical features, diagnosis, treatment / A. L. Shulzhenko, I. N. Zuikova. Cervix, vagina, vulva. Physiology, pathology, colposcopy, aesthetic correction. Guidelines for clinicians. ed. by S. I. Rogovskaya, E. V. Lipova. – Moscow: StatusPraesens, 2014. – P. 456-475. DOI: 10.1055/s-0042-116494
27. miR-130a/TGF-β1 axis is involved in sow fertility by controlling granulosa cell apoptosis. X. Du, L. Wang, Q. Li, W. Wu [et al.] Theriogenology. – Vol. 157. – pp. 407–417. DOI: 10.1016/j.theriogenology.2020.08.015

Authors
Tatiana A. Nevezhkina
Pacific state medical university (FSBEI HE PSMU MOH Russia, Vladivostok)
Associate professor of normal and pathological physiology department
2 Ostryakov ave. Vladivostok Russian Federation 690002
tanya.ru9292@mail.ru

E.V. Markelova
Pacific state medical university (FSBEI HE PSMU MOH Russia, Vladivostok)
MD, Professor, Head of the department of normal and pathological physiology
2 Ostryakov ave. Vladivostok Russian Federation 690002

S.V. Knysh
Pacific state medical university (FSBEI HE PSMU MOH Russia, Vladivostok)
Ph.D. (medicine), Assistant professor of normal and pathological physiology department
2 Ostryakov ave. Vladivostok Russian Federation 690002

M.S. Tulupova
Paracelsus LLC, Vladivostok
Ph.D. (medicine), Chief Physician
4A st. Novoivanovskaya Vladivostok Russian Federation

L.S. Matyshkina
Pacific state medical university (FSBEI HE PSMU MOH Russia, Vladivostok)
Ph.D. (medicine), associate professor, head of obstetrics and gynecologist department
2 Ostryakov ave. Vladivostok Russian Federation 690002

 

 
 
 

Authorization