Effects of aminoglycosides on macrophage viability and antimicrobial function under high-glucose exposure

High-glucose exposure is associated with impaired innate immune function and increased susceptibility to infection; however, its influence on antibiotic–macrophage interactions remains incompletely understood. This study investigated the context-dependent effects of the aminoglycosides streptomycin and kanamycin on murine RAW 264.7 macrophages under low-glucose (5.5 mM) and high-glucose (25 mM) exposure conditions, used to simulate normoglycemic and hyperglycemic environments. Macrophage viability, phagocytic activity, intracellular bacterial killing, and expression of pro-inflammatory mediators were evaluated following exposure to Escherichia coli ATCC 25922. High-glucose conditions significantly reduced macrophage phagocytosis and intracellular bacterial killing and increased the expression of IL-1β, IL-6, TNF-α, and iNOS. Neither streptomycin nor kanamycin restored phagocytic activity or altered inflammatory gene expression under either glucose condition. In contrast, both aminoglycosides significantly enhanced intracellular bacterial killing under high-glucose exposure, despite persistent impairment of phagocytosis. Cytotoxicity assessments presented concentration-dependent effects of both antibiotics, with macrophage viability preserved at concentrations corresponding to 1× and 2× minimum inhibitory concentration under both glucose conditions. Together, these results indicate that high-glucose exposure is associated with impaired macrophage antimicrobial activity, while aminoglycosides preserve the ability to enhance intracellular bacterial killing under high-glucose exposure without implying direct immunomodulatory effect. This observation underscores the influence of high-glucose environments on antibiotic–host cell interactions.