Dezocine mitigates LPS-induced acute lung injury by regulating alveolar macrophage polarization

Acute lung injury (ALI) or its more severe form, acute respiratory distress syndrome, is a life-threatening disease closely associated with an imbalance of M1/M2 macrophage polarization. Dezocine is commonly used clinically for perioperative pain relief, but whether it can regulate lipopolysaccharide (LPS)-induced alveolar macrophage polarization is unclear. This study aimed to determine the effect of dezocine on ALI and its potential ability to modulate macrophage polarization in ALI mouse models. The male C57BL/6 mouse were randomly divided into four groups: Control group, dezocine (DEZ) group, LPS group, and LPS + DEZ group. Samples were collected at 24 h after treatment to evaluate lung injury, inflammatory status and alveolar macrophage polarization. Dezocine ameliorated the severity of ALI, lung wet-to-dry (W/D) weight ratio, and lung injury scores. Additionally, dezocine inhibited M1 polarization and promoted M2 polarization of alveolar macrophages, including the downregulation of M1-related markers (CD86) in lung tissue, the decrease of pro-inflammatory factors (interleukin-6, IL-6 and tumor necrosis factor-α, TNF-α) in serum and bronchoalveolar lavage fluid (BALF), the upregulation of M2-related markers (CD206) in lung tissue, the increase of ant-inflammatory factors(interleukin-10, IL-10 and transforming growth factor-β, TGF-β) in serum and BALF. These findings indicate that dezocine alleviates lung injury and exerts anti-inflammatory effects by modulating alveolar macrophage polarization balance, suggesting that dezocine might act as a novel anti-inflammatory drug for treating ALI and hence provide a promising strategy for enhanced the therapy in the clinic.