Severe bacterial infections (e.g., pneumonia, sepsis) serve as key contributors to acute lung injury (ALI), underscoring the necessity of concurrent anti-infective therapy. The pathogenesis of ALI primarily mediates through two intertwined pathological processes: oxidative stress and cytokine storm. Minocycline, a semisynthetic tetracycline derivative with established clinical applications, exhibits promising potential as a therapeutic candidate for ALI due to its anti-inflammatory and antioxidant pharmacological actions. This investigation employed the lipopolysaccharide (LPS)-induced ALI mice model and RAW264.7 cells inflammation model to evaluate the pulmonary protective effects of minocycline. Our findings demonstrated that minocycline ameliorated symptoms of ALI in LPS-induced mice, including attenuating inflammatory cell infiltration, suppressing cytokine storm, mitigating oxidative stress damage, alleviating pulmonary edema and reducing microvascular permeability. Parallel in vitro experiments revealed that minocycline exhibited inhibitory effects on inflammatory response and oxidative stress in LPS-stimulated RAW264.7 cells. These results suggested that minocycline attenuated cytokine storm and oxidative stress, thereby protecting mice against lung injury. Therefore, minocycline may offer superior benefits compared to other antibiotics for ALI patients infected with susceptible bacteria. While preclinical investigations have unveiled emerging clinical application prospects, rigorous clinical trials remain imperative to substantiate minocycline's therapeutic efficacy in human populations.
Keywords: Acute lung injury; Cytokine storm; Drug repurposing; Minocycline; Oxidative stress; Sepsis.
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