Khryanin A A, Sturov V G
Novosibirsk State Medical University of the Ministry of Health of Russian Federation, Novosibirsk, Russia.
Novosibirsk National Research State University, V. Zelaman Institute of Medicine and Psychology, Novosibirsk, Russia.
Urologiia. 2020 Sep(4):36-44.
Assessment of the severity of immunological disorders in patients with hlamydia trachomatis (CT) infection and the effectiveness of antibacterial therapy in combination with systemic enzyme therapy for the eradication of pathogenic pathogen and correction of detected violations of the immune system.
84 patients with identified CT infection were divided into 2 clinical groups: group 1 (42 people) received antibiotic therapy with doxycycline monohydrate for 10 days, 100 mg 2 times a day (the first dose of 200 mg) at regular intervals (daily dose of 200 mg, course - 2.0 g.) in combination with phlogenzyme, 3 tablets 2 times a day within 14 days. The second clinical group (42 people) received only doxycycline monohydrate therapy at the same doses as in the first clinical group. In all patients with CT infection (84 people) and in the control group (32 practically healthy people), the activity of immune reac-tions in the body was additionally assessed by the level of cytokines (-INF, IL-1, IL-4, IL-6), circulating immune complexes (CIC), lactoferrin (LF) and 2-macroglobulin in blood serum.
The level of CEC in the blood serum of patients with CT infection is significantly higher than the standard indicators (by 1.83 times) compared with the indicators of the control group (106.1+/-5.12 conventional units versus 57.8+/-3.39 conventional units, p<0.05). The level of -IFN in the blood serum of patients with CT infection is 1.64 times lower than in the control (28.9+/-4.15 pkg / ml and 47.3+/-4.26 pkg / ml, p<0.05), and indicators of IL-1 in blood serum - 3.12 times higher; the level of IL-6 is 2.13 times higher (p<0.001); the level of IL-4 is 1.65 times higher (p<0.05). The Lf level in patients with CT infection exceeded 2.37 times the indicator in the control group (1742.0+/-112.15 ng / ml and 732.1+/-36.11 ng / ml, p<0.001), 2-macroglobulin - in 1, 36 times (2.59 - 0.21 mg/l and 1.9 - 0.47 mg / l, p<0.001). The efficiency of clinical and microbiological cure in patients with CT infection, who received complex therapy with doxycycline monohydrate and phlogenzyme, was 97.6%. With monotherapy (doxycycline monohydrate), the effectiveness of clinical and microbiological cure was significantly lower - 78.6%, statistically significant (OR=11.2; 95% CI 1.3-247.9; p=0.007). The fact of a decrease in the activity of Th-2 type of the cellular link of immunity in patients with CT infection receiving systemic enzyme therapy drug was established.
One of the pathogenetic mechanisms of CT infection is an imbalance in the cytokine profile, which manifests itself in an increase in the level of cytokines of the Th-2 (IL-6) type and a decrease in the Th-1 (-IFN) type. With the predominant production of pro-inflammatory cytokines (IL-1, IL-6), the dynamics of CT infection becomes chronic. A decrease in the reserve capacity of the proteolytic enzyme system during CT infection with a subsequent increase in the level of 2-macroglobulins in the blood contributes to the dysregulation of local inflammation processes and the formation of immune disorders. With a long course of CT infection, it is most advisable to use (as a basic pathogenetic therapy) systemic enzyme therapy (phlogenzyme). The effect of systemic enzyme therapy on immune responses in C. trachomatis enhances the activity of the Th-1 type of cytokines (-IFN) and a decrease in the level of 2-macroglobulins and pro-inflammatory cytokines (IL-1, IL-6) in the blood. Systemic enzyme therapy can significantly increase the effectiveness of antibiotic therapy and reduce the risk of side effects.
The theoretical argumentation of the pathophysiological mechanisms of disorders in the interaction of the most important functional systems made it possible to substantiate new conceptual approaches to the therapy of CT infection, taking into account the level and specific disorders in the universal systems of homeostasis regulation. In particular, a pathophysiological basis has been provided to substantiate the advisability of combining antibacterial therapy with systemic enzyme therapy drugs to correct systemic immunological disorders in patients with CT infection.
评估沙眼衣原体(CT)感染患者免疫紊乱的严重程度,以及抗菌治疗联合全身酶疗法根除致病病原体和纠正检测到的免疫系统异常的有效性。
84例确诊为CT感染的患者分为2个临床组:第1组(42人)接受为期10天的多西环素单水合物抗生素治疗,每天2次,每次100mg(首剂200mg),间隔规律(日剂量200mg,疗程 - 2.0g),并联合phlogenzyme,每天2次,每次3片,共14天。第二临床组(42人)仅接受与第一临床组相同剂量的多西环素单水合物治疗。对所有CT感染患者(84人)和对照组(32名实际健康者),通过血清中细胞因子(-INF、IL-1、IL-4、IL-6)、循环免疫复合物(CIC)、乳铁蛋白(LF)和2-巨球蛋白水平额外评估体内免疫反应活性。
与对照组相比,CT感染患者血清中CEC水平显著高于标准指标(高1.83倍)(106.1±5.12传统单位 vs 57.8±3.39传统单位,p<0.05)。CT感染患者血清中-IFN水平比对照组低1.64倍(28.9±4.15pg/ml和47.3±4.26pg/ml,p<0.05),血清中IL-1指标高3.12倍;IL-6水平高2.13倍(p<0.001);IL-4水平高1.65倍(p<0.05)。CT感染患者的Lf水平超过对照组指标2.37倍(1742.0±112.15ng/ml和732.1±36.11ng/ml,p<0.001),2-巨球蛋白 - 高至1.36倍(2.59 - 0.21mg/l和1.9 - 0.47mg/l,p<0.001)。接受多西环素单水合物和phlogenzyme联合治疗的CT感染患者临床和微生物学治愈效率为97.6%。单药治疗(多西环素单水合物)时,临床和微生物学治愈有效性显著较低 - 78.6%,具有统计学意义(OR=11.2;95%CI 1.3 - 247.9;p=0.007)。接受全身酶疗法药物的CT感染患者中,免疫细胞Th-2型活性降低这一事实得到证实。
CT感染的发病机制之一是细胞因子谱失衡,表现为Th-2(IL-6)型细胞因子水平升高和Th-1(-IFN)型细胞因子水平降低。当促炎细胞因子(IL-1、IL-6)占主导产生时,CT感染的病程会变为慢性。CT感染期间蛋白水解酶系统储备能力下降,随后血液中2-巨球蛋白水平升高,这有助于局部炎症过程的失调和免疫紊乱的形成。对于CT感染的长期病程,最适宜使用(作为基本的发病机制治疗)全身酶疗法(phlogenzyme)。全身酶疗法对沙眼衣原体免疫反应的影响增强了Th-1型细胞因子(-IFN)的活性,并降低了血液中2-巨球蛋白和促炎细胞因子(IL-1、IL-6)的水平。全身酶疗法可显著提高抗生素治疗的有效性并降低副作用风险。
对最重要功能系统相互作用中紊乱的病理生理机制进行理论论证,使得考虑内稳态调节通用系统中的水平和特定紊乱,为CT感染治疗证实新的概念性方法成为可能。特别是,已提供病理生理基础以证实抗菌治疗与全身酶疗法药物联合使用以纠正CT感染患者全身免疫紊乱的合理性。