Papillomaviruses are a group of DNA viruses belonging to the Papillomavirida family. These viruses provoke pathological conditions manifesting with inflammation, exophytic masses, carcinogenesis, reproductive and perinatal disorders. Immune status is an essential factor de-termining the severity and duration of inflammatory diseases, the course of latent viral infections, including papillomavirus infection (PVI). The human immune system prevents the persistence, reactivation, and development of PVI clinical presentations. The cellular immune response is realized under the control of interferons (IFNs). Today, no complex studies on type 1, 2, or 3 IFNs in the cervical mucus of women with PVI associated with herpesvirus and chlamydia infec-tions are available. Aim: to compare IFN profile of mucosal immunity in women with PVI associated with herpesvirus and chlamydia infections. Patients and Methods: this study enrolled 149 women aged 25–44. Women were divided into four groups. Group 1 included women with PVI only (n=21). Group 2 included women with PVI and herpesvirus infection (n=47). Group 3 included women with PVI and chlamydia infec-tions (n=39). Group 4 included controls (n=30). Complex outpatient clinical laboratory examina-tion included clinical functional, biochemical, and immunological tests to detail pathophysiolog-ical mechanisms of urogenital PVIs. IFN (IFN-β, IFN-γ, IFN-λ1/IL-29, IFN-λ3/IL-28B) levels in the cervical mucus were measured by ELISA. Results: in all groups, IFN-λ3 and IFN-γ deficiencies were detected. In PVI, IFN-γ deficiency prevailed. In PVI associated with herpesvirus infection, IFN-λ3 deficiency prevailed. In PVI associated with chlamydia infection, a severe IFN-β deficiency was revealed. Conclusion: these patterns demonstrate a relevant role of the interferon arm of the im-mune response in the pathogenesis of isolated PVI and PVI associated with herpesvirus and chlamydia infections. These alterations in mucosal immunity support the prescription of immu-notherapy for these infections. KEYWORDS: human papillomavirus, herpesvirus infection, chlamydia infection, interferons, immune system, cervical mucus, mucosal immunity. FOR CITATION: Markelova E.V., Tulupova M.S., Nevezhkina T.A. et al. Interferon profile of the mucosal immunity in women with papillomavirus infection. Russian Medical Inquiry. 2022;6(2):67–71 (in Russ.). DOI: 10.32364/2587-6821-2022-6-2-67-71.
Вирус иммунодефицита человека (ВИЧ) способен вызывать состояние иммуносупрессии, которая обусловливает реактивацию цитомегаловируса и других ассоциированных с ним скрытых заболеваний. В этой работе изучаются показатели системы интерферонов как важных участников противовирусной защиты врожденного иммунитета. Проведено исследование уровня ИФН-γ, ИФН-λ1 (ИЛ-29), ИФН-λ3 (ИЛ-28В), ФНО-α и ИЛ-10 в сыворотке крови у ВИЧ-положительных пациентов с цитомегаловирусной инфекцией (ЦМВ). Были обследованы 142 пациента, находящихся на стационарном лечении, с диагнозом «ВИЧ-инфекция, 4а стадия», за период с 2016 по 2021 гг., из них 63 -с сопутствующей ЦМВИ, мужского пола, средний возраст 30 лет (21-40 лет). Группа контроля: 30 практически здоровых добровольцев, сопоставимых по возрасту. Определение уровней ИФН-γ, ИЛ-29, ИЛ-28В, ФНО-α и ИЛ-10 в сыворотке венозной крови проводили методом твердофазного иммуноферментного анализа. Пациенты ретроспективно были разделены на 2 группы. I группа -79 пациентов с ВИЧ, II (ГК) -63 с ВИЧ и ЦМВ. Наличие активной инфекции подтверждалось позитивной ПЦР и наличием антител классов IgG и IgM в сыворотке крови, а также определением индекса авидности антител IgG. В группах пациентов с ВИЧинфекцией и ЦМВ значения ИФН-γ, ИЛ-29 (ИФН-λ1) и ИЛ-28В (ИФН-λ3) были снижены в 3-10 раз по сравнению с группой контроля. В группах пациентов с ВИЧ-инфекцией, как с ЦМВ, так и без него, коэффициенты ФНО-α/ИЛ-10, а также значения ИФН-γ, ИЛ-29 (ИФН-λ1) были выше по сравнению с ГК. ФНО-α и ИЛ-10, были повышены у пациентов I и II групп по сравнению с ГК. В I группе уровень ФНО-α был выше, чем в II группе.
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.
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