COMPARATIVE ASSESSMENT OF THE IMPACT OF INTERFERONOGENIC PREPARATIONLARIFAN ON MONOCYTES FROM AGED C57BL/6 AND BALB/C MICE IN VITRO
DOI: 10.17721/1728.2748.2024.98.5-10
Keywords:
bacteriophage-derived dsRNA, blood monocytes, phagocytic activity, reactive oxygen species, CD80, CD206Abstract
Background. Blood monocytes play a crucial role in immunity as effector cells of innate immunity. However, they can also promote hyperinflammation, as was described in COVID-19. Many viral infections trigger hyperinflammation by inhibiting type I interferon synthesis, necessitating search of interferon-based or interferonogenic treatments like Larifan – bacteriophagederived dsRNA with interferonogenic and immunomodulatory properties. Global statistics indicate that viral infections, including SARS-CoV-2, as well as hyperinflammation occur more frequently in males, especially in the older age group, and significantly depends on genetically determined profile of immune reactivity. The aim of this study was a comparative assessment of the impact of Larifan on the metabolic profile of peripheral blood monocytes from aged male C57BL/6 and BALB/c mice in vitro.
Methods. Male aged C57BL/6 and BALB/c mice were used in this study. Blood samples were collected from facial vein and treated with Larifan in vitro. Phagocytic activity, ROS production, and expression of phenotypic markers were assessed by flow cytometry. Only live monocytes were gated and included in the analysis. Data are presented as median and interquartile range (IQR). Statistical differences were calculated using Kruskal–Wallis test, with significance set at p < 0.05.
Results. BALB/c mice showed a lower baseline phagocytic index than C57Bl/6, but phagocytosis percentages were comparable. Treatment with Larifan reduced the phagocytosis percentage in both strains, yet the phagocytic index rose in BALB/c mice after dsRNA exposure. ROS production was higher in C57Bl/6 mice, with Larifan reducing ROS levels significantly in both strains. CD80 baseline expression levels were higher in BALB/c, and dsRNA increased CD80-positive cells as well as decreased expression level of CD80 in BALB/c mice only. CD206 expression was lower in BALB/c but unaffected by Larifan, while dsRNA reduced both number of CD206-positive cells and CD206 levels in C57Bl/6 mice.
Conclusions. The metabolic profile of monocytes differs between Th1-dominant C57Bl/6 and Th2-biased BALB/c mice, with higher baseline indicators in C57Bl/6 mice. Larifan treatment exerts anti-inflammatory effects by reducing ROS synthesis in both strains, with BALB/c mice also displaying increased phagocytosis and reduced antigen-presenting capability
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