Strategies for Using Muramyl Peptides - Modulators of Innate Immunity of Bacterial Origin - in Medicine

Abstract

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.

Dual Effect of Low-Molecular-Weight Bioregulators of Bacterial Origin in Experimental Model of Asthma

“…A similar decrease in IgE with the advance administration of LPS and GMDP prior to antigen sensitization explains the positive effect of the treatment of asthma and atopic diseases using GMDP, obtained in clinical practice [57][58][59]. Asthma is known to be caused primarily by the binding of complexes of the allergen and allergen-specific IgE to their receptors on antigen-presenting cells and the presentation of the processed allergen to T cells.…”

Exploring the mechanism and experimental verification of puerarin in the treatment of endometrial carcinoma based on network pharmacology and bioinformatics analysis

“…GO enrichment analysis suggested that it was significantly enriched in the “response to LPS” and “response to bacterial molecular sources”. Cytowall peptides, as a known component of peptidoglycan, can participate in hematopoietic processes and stimulate the production of colony-stimulating factors for the treatment of tumor cells [ 25 ]. At the same time, LPS functions as a major component of the cell wall of Gram-negative bacteria, which can be recognized by TLR-4 and alter the immune response in different cancer patients [ 26 , 27 ].…”

Immunomodulatory and Allergenic Properties of Antimicrobial Peptides

“…Defensin secretion is induced both by whole bacteria and by their components, for example, by LPS, lipoteichoic acid, lipid A, and muramyl peptides [ 115 , 116 , 117 ]. After it was shown that CpG oligodeoxynucleotides also induce the secretion of defensins, it became obvious that stimulation of the TLR or NLR receptors of the innate response is the signal for the release of defensins by cells [ 118 , 119 , 120 ].…”