Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences (RAS), Moscow, Russia.
Department of Biology and General Genetics, Medical Institute, RUDN University, Moscow, Russia.
Front Immunol. 2021 Apr 20;12:607178. doi: 10.3389/fimmu.2021.607178. eCollection 2021.
The spread of infectious diseases is rampant. The emergence of new infections, the irrational use of antibiotics in medicine and their widespread use in agriculture contribute to the emergence of microorganisms that are resistant to antimicrobial drugs. By 2050, mortality from antibiotic-resistant strains of bacteria is projected to increase up to 10 million people per year, which will exceed mortality from cancer. Mutations in bacteria and viruses are occurring faster than new drugs and vaccines are being introduced to the market. In search of effective protection against infections, new strategies and approaches are being developed, one of which is the use of innate immunity activators in combination with etiotropic chemotherapy drugs. Muramyl peptides, which are part of peptidoglycan of cell walls of all known bacteria, regularly formed in the body during the breakdown of microflora and considered to be natural regulators of immunity. Their interaction with intracellular receptors launches a sequence of processes that ultimately leads to the increased expression of genes of MHC molecules, pro-inflammatory mediators, cytokines and their soluble and membrane-associated receptors. As a result, all subpopulations of immunocompetent cells are activated: macrophages and dendritic cells, neutrophils, T-, B- lymphocytes and natural killer cells for an adequate response to foreign or transformed antigens, manifested both in the regulation of the inflammatory response and in providing immunological tolerance. Muramyl peptides take part in the process of hematopoiesis, stimulating production of colony-stimulating factors, which is the basis for their use in the treatment of oncological diseases. In this review we highlight clinical trials of drugs based on muramyl peptides, as well as clinical efficacy of drugs mifamurtide, lycopid, liasten and polimuramil. Such a multifactorial effect of muramyl peptides and a well-known mechanism of activity make them promising drugs in the treatment and preventing of infectious, allergic and oncological diseases, and in the composition of vaccines.
传染病的传播猖獗。新感染的出现、医学中抗生素的不合理使用以及其在农业中的广泛应用导致了对抗生素药物具有耐药性的微生物的出现。到 2050 年,预计因对抗生素耐药细菌菌株的死亡率将增加到每年 1000 万人,超过癌症死亡率。细菌和病毒的突变速度比新药物和疫苗推向市场的速度更快。为了寻找针对感染的有效保护,正在开发新的策略和方法,其中之一是使用先天免疫激活剂与病因化疗药物联合使用。肽聚糖是所有已知细菌细胞壁的一部分,在微生物群落分解过程中,体内经常会形成肽聚糖,被认为是天然的免疫调节剂。它们与细胞内受体的相互作用会引发一系列的过程,最终导致 MHC 分子、促炎介质、细胞因子及其可溶性和膜相关受体的基因表达增加。结果,所有免疫活性细胞亚群都被激活:巨噬细胞和树突状细胞、中性粒细胞、T 细胞、B 细胞和自然杀伤细胞,以对异源或转化抗原产生适当的反应,这表现在炎症反应的调节和提供免疫耐受方面。肽聚糖参与造血过程,刺激集落刺激因子的产生,这是其在治疗肿瘤疾病中的应用基础。在这篇综述中,我们重点介绍了基于肽聚糖的药物的临床试验,以及米夫莫肽、利卡培南、利奥西肽和波利姆瑞肽的临床疗效。肽聚糖的这种多效性作用和众所周知的作用机制使它们成为治疗和预防感染、过敏和肿瘤疾病以及疫苗组成的有前途的药物。