合成胸腺六肽在纠正局部无限急性腹膜炎免疫受损儿童的抗菌免疫防御改变和促炎细胞因子谱正常化中的作用

Svetlana V. Kovaleva, V. N. Chapurina, L. Lomtatidze, D. E. Lyagusha, Yu. V. Teterin, N. K. Barova, K. I. Melkonyan
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引用次数: 0

摘要

研究严重化脓性炎症疾病(PIDs)免疫发病机制背后的免疫系统调节紊乱,对于开发恢复抗菌防御的新疗法非常重要。急性腹膜炎(AP)是一种严重的腹腔化脓性炎症,其病程取决于治疗、细胞因子平衡和免疫系统的充分运作。目的:评估合成胸腺六肽(伊莫诺凡的活性物质)对免疫系统和促炎细胞因子水平的调节作用。对 20 名患有局部 AP 的 5-12 岁免疫力低下儿童(研究组 1,SG1)和 20 名条件健康儿童(对比组,SG)分别进行了 CPOT(包括合成胸腺六肽(精氨酰-α-天冬氨酰-赖氨酰-缬氨酰-酪氨酰-精氨酰,НР))之前(研究组 1a,SG1a)和之后(研究组 1a,SG1a)的临床和免疫学检查。对 T 和 B 淋巴细胞、自然杀伤细胞(NK)的含量、血清促炎细胞因子 IL-1β、IL-6、TNFα、IL-8、IL-18 的水平、中性粒细胞(NG)的吞噬和杀微生物活性进行了评估。在治疗前的 SG1 中,T 淋巴细胞、T 辅助淋巴细胞、CTL 淋巴细胞、NK 的数量减少,而 B 淋巴细胞的数量增加。研究还发现了 NG 的效应功能缺陷:细菌抗原杀伤力减弱和 NADPH 氧化酶活性降低。研究发现,免疫力低下儿童发生 AP 时,细胞因子谱的特点是所研究的促炎细胞因子和中性粒细胞相关细胞因子过度分泌。经过包括免疫调节疗法在内的综合治疗后,T 淋巴细胞、T 辅助细胞、TCTL 淋巴细胞的含量得到恢复,NK 数量增加,B 淋巴细胞水平下降。此外,由于 NADPH 氧化酶活性的恢复,炎症细胞因子(包括中性粒细胞相关细胞因子)的水平也有所下降,NG 的效应功能也有所显现。因此,AP 免疫学参数的恢复导致腹腔化脓性炎症过程提前消退,并避免了术后并发症。以 HP 为基础的药物免疫调节治疗方案的临床和免疫学效果决定了其在患有局部 AP 的免疫功能低下儿童术后使用的可行性。
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Synthetic thymic hexapeptide in the correction of alterations of antibacterial immune defense and normalization of the profile of proinflammatory cytokines in immunocompromized Children with local unlimited acute peritonitis
The study of dysregulatory disorders of the immune system underlying the immunopathogenesis of severe purulent-inflammatory diseases (PIDs) is important for development of new therapeutic tactics of restoring antibacterial defense. Acute peritonitis (AP) is a severe PID of the abdominal cavity, the course of which are dependent on the treatment, cytokine balance and adequate functioning of the immunity. Objective: to evaluate the modulating effects on the immune system and the levels of proinflammatory cytokines of the synthetic thymic hexapeptide, active substance of Imunofan, included in the complex postoperative treatment (CPOT) of immunocompromised children with local AP. Clinical and immunological examination of 20 immunocompromised children aged 5–12 years with local AP was carried out before (study group 1, SG1) and after (study group 1a, SG1a) CPOT including synthetic thymic hexapeptide (Arginyl-alpha-AspartylLysyl-Valyl-Tyrosyl-Arginine, НР), alongside 20 conditionally healthy children (comparison group, SG). The content of T and B lymphocytes, natural killer cells (NK), levels of serum pro-inflammatory cytokines IL-1β, IL-6, TNFα, IL-8, IL-18, phagocytic and microbicidal activity of neutrophils (NG) were assessed. In SG1, before treatment, a decrease in the number of T lymphocytes, T helpers, CTL-lymphocytes, NK and an increase in the level of B lymphocytes was revealed. Defects in the effector functions of NG were determined: impaired bacterial antigen killing and decreased NADPH oxidase activity. It was established that in case of AP in immunocompromised children, the cytokine profile is characterized by overproduction of studied proinflammatory and neutrophil-associated cytokines. After complex treatment including immunomodulatory therapy, there was a restoration of the content of T lymphocytes, T helper cells, TCTL lymphocytes, an increase in the number of NK and decrease in the level of B lymphocytes. In addition, regression of the levels of inflammatory, including neutrophil-associated, cytokines and emergence of effector functions of NG due to restoration of NADPH oxidases activity, was noted. Thus, the restoration of immunological parameters in AP leads to earlier regression of the purulent-inflammatory process in the abdominal cavity and to the absence of postoperative complications. The clinical and immunological effects of the immunomodulatory therapy program with inclusion of the drug based on HP determines the feasibility of its use in the postoperative period in immunocompromised children with local AP.
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