Exploring the Therapeutic Potential of Antibiotics in Hyperglycemia-Induced Macrophage Dysfunctions

Background: Diabetes mellitus exacerbates immune dysfunction, leading to higher susceptibility to infections. This study investigated the effects of antibiotics on macrophage functions under high glucose conditions to mimic a diabetic context. Methods: Using murine macrophage cell line RAW 264.7, the present study evaluated the cytotoxicity, phagocytosis, bactericidal activity, and pro-inflammatory cytokine production after treatment with four antibiotics: oxytetracycline, ciprofloxacin, sulfamethoxazole–trimethoprim, and cefotaxime. Results: All antibiotics demonstrated no cytotoxicity across 1×–8× MIC concentrations. Hyperglycemia significantly impaired macrophage phagocytosis and bactericidal activity while inducing pro-inflammatory mediator markers, IL-1, IL-6, TNF-α, and iNOS. Only ciprofloxacin significantly improved phagocytic achieving levels comparable to the low glucose control. Treatments with ciprofloxacin, sulfamethoxazole–trimethoprim, and cefotaxime significantly enhanced bactericidal activity without altering the pro-inflammatory cytokine profile. Conclusions: These findings underscore the negative effect of high glucose on macrophage functions and suggest that ciprofloxacin may be a potential therapeutic option for diabetes-associated infections.