Clinical and immunological efficacy of the immunomodulating hexapeptide arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine in the complex postoperative treatment of children with acute osteomyelitis

Galina A. Chudilova, E. A. Chicherev, Yu. V. Teterin, V. N. Chapurina, V. A. Tarakanov, N. K. Barova, I. V. Nesterova
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Abstract

The recurrent and persistent nature of osteomyelitis, like as associated high morbidity of patients, prolonged hospitalization and expensive treatment require development of new approaches in therapy and pathogenetic justification of the immunotropic drugs usage in complex etiopathogenetic treatment of this disorder. Our objective was to evaluate the clinical and immunological efficacy of hexapeptide (HP), arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine implemented in the complex treatment of acute osteomyelitis in children during the postoperative period. 19 children aged 8-15 years with acute osteomyelitis (AOM) were studied: the study group 1 (SG1, n = 11) received a standard treatment at all the disease stages; in study group 2 (SG2, n = 8), the standard therapy was supplemented with a medical drug Imunofan, containing hexapeptide (НP) as the active substance. Prior and after the course of drug treatment, we determined the following parameters: the contents of T cells (CD3+CD19-, CD3+CD4+, CD3+CD8+, CD3+CD4+/CD3+CD8+) and B cells (CD3-CD19+), NK (CD3-CD16+CD56+) by means of Cytomics FC-500 (Веckman Coulter, USA), the levels of serum IgA, IgM, IgG (ELISA tests), assessment of phagocytic activity of neutrophil granulocytes (NG) with determining the ratio of actively phagocytic NG (%PhAN), capture processes (PhN, PhI) and the completeness of phagocytosis (%D, DI) tested with S. aureus (strain No. 209). In the studied groups with AOM, a decreased content of T lymphocytes, T helper cells, T lymphocytes, NK cells was revealed, along with unchanged content of B lymphocytes. In SG2, the increased IgA and IgG levesl have been shown. We have also revealed a deficiency of phagocytic function associated with the processes of phagocytosis completion. The use of immunomodulatory therapy with an HP-containing pharmaceutical drug in combination with standard treatment was associated with restoration of immunological parameters to the reference values of healthy children, thus leading to shorter febrile period, milder manifestations of intoxication, earlier periods of reconvalescence from purulent-inflammatory process, and reduced hospital stay. The obtained positive clinical and immunological effects demonstrate the expediency of targeted immunomodulatory therapy including a pharmaceutical HP-containing drug as the active substance in the complex postoperative treatment of children with AOM. Restoration of the disturbed mechanisms of anti-infectious immunity in AOM under usage of immunomodulating HP contributes to more effective elimination of pathogens and, as a result, improvement of the clinical course of the disease, as well as prevention of chronic inflammatory processes and aggravation of immune system dysfunction.
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免疫调节六肽精氨酸- α -天冬氨酸-赖氨酸-缬氨酸-酪氨酸-精氨酸在小儿急性骨髓炎术后复杂治疗中的临床及免疫学疗效
骨髓炎的复发性和持续性,如相关患者的高发病率、长期住院和昂贵的治疗,需要开发新的治疗方法和在复杂的病因学治疗中使用免疫药物的病理合理性。我们的目的是评估六肽(HP),精氨酸- α -天冬氨酸-赖氨酸-缬氨酸-酪氨酸-精氨酸在儿童术后急性骨髓炎综合治疗中的临床和免疫学疗效。研究了19名8-15岁急性骨髓炎(AOM)儿童:研究组1 (SG1, n = 11)在所有疾病阶段接受标准治疗;研究2组(SG2, n = 8)在标准治疗的基础上加用含六肽(НP)为活性物质的医用药物免疫凡。在药物治疗前后,我们确定了以下参数:利用流式细胞仪FC-500 (Веckman Coulter, USA)检测T细胞(CD3+CD19-、CD3+CD4+、CD3+CD8+、CD3+CD4+/CD3+CD8+)和B细胞(CD3-CD19+)、NK细胞(CD3- cd16 +CD56+)的含量,ELISA检测血清IgA、IgM、IgG的水平,用金黄色葡萄球菌(菌株209)检测中性粒细胞(NG)的吞噬活性,测定活性吞噬NG的比例(%PhAN)、捕获过程(PhN、PhI)和吞噬的完整性(%D、DI)。AOM组T淋巴细胞、T辅助细胞、T淋巴细胞、NK细胞含量降低,B淋巴细胞含量不变。在SG2中,IgA和IgG水平升高。我们还揭示了与吞噬完成过程相关的吞噬功能缺陷。采用含hp药物的免疫调节治疗联合标准治疗,可使健康儿童的免疫参数恢复到参考值,从而缩短发热期,减轻中毒症状,提前从脓性炎症过程中恢复,缩短住院时间。所获得的积极的临床和免疫学效果表明,包括含hp药物作为活性物质的靶向免疫调节治疗在AOM患儿复杂的术后治疗中的便宜性。在免疫调节HP的作用下,恢复AOM中被干扰的抗感染免疫机制,有助于更有效地消除病原体,从而改善疾病的临床病程,并预防慢性炎症过程和免疫系统功能障碍的加重。
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