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DOI: 10.18413/2658-6533-2023-9-3-0-6

Effect of pyrimidine derivative on cytokine levels in experimental generalized staphylococcal infection

Background: To date, bacterial infections caused by microorganisms characterized by antibiotic resistance are one of the leading causes of the protracted course of infectious and inflammatory diseases that occur with the development of a systemic inflammatory reaction. It is proved that the severity of infectious pathology is caused by hyperproduction of proinflammatory cytokines, which can lead to the development of the so-called "cytokine storm" with the subsequent development of multiple organ failure. Considerable efforts have been made to overcome this problem, including the development of new effective antimicrobial drugs capable of having an immunoregulatory effect. Currently, pyrimidine heterocyclic compounds are considered as the main group of substances for their use as a basis for medicines. The aim of the study: Evaluation of the effect of pyrimidine derivative 3-(2-Phenyl-2-oxoethyl)-quinazoline-4(3H)-one on the level of cytokines in experimental generalized staphylococcal infection. Materials and methods: The effect of pyrimidine derivative on the level of pro- and anti-inflammatory cytokines was evaluated on a model of generalized infection caused by intraperitoneal administration of Staphylococcus aureus to mice at a dose of 108 microbial bodies. 5-week-old mice (40 individuals) were divided into the groups: control I – animals receiving intraperitoneal water for injection; control II – mice infected with staphylococcus who did not receive treatment; two experimental groups were mice that received intraperitoneal ceftriaxone at an average therapeutic dose of 50 mg/kg and pyrimidine compound at a dose of 21 mg/kg. The level of pro- and anti-inflammatory cytokines in blood serum was determined by enzyme immunoassay. Results: Pyrimidine derivative 3-(2-Phenyl-2-oxoethyl)-quinazoline-4(3H)-one on led to a decrease in the level of proinflammatory cytokines; it was found that the data the changes were less pronounced in comparison with the group of animals receiving the comparison drug – ceftriaxone. The introduction of a pyrimidine derivative led to an increase in the level of anti-inflammatory interleukins (IL-4, IL-10) compared with control II. Conclusion: The results obtained indicate that the studied compound has a regulatory effect on the cytokine profile and possible activation of mechanisms that contribute to the suppression of the infectious agent.

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