Available online 3 June 2022, 104557

• High-dose metformin promotes M1 pro-inflammatory macrophage polarization from monocytes derived from human cord blood.

• Low-dose metformin enhances an anti-inflammatory response by favoring M2 macrophage polarization.

• Low-dose metformin administration induces M2 expansion in a BPD model.

While the association of inflammation with bronchopulmonary dysplasia (BPD) has long been appreciated, M1 proinflammatory macrophage population is emerging as the key element in driving the BPD inflammatory environment. Previous study suggests that low-dose metformin elicits an anti-inflammatory response, possibly through modulating macrophages, to improve disease outcome in a rat BPD model. To investigate this concept further, we examined the dose-dependent immunomodulatory function of metformin directly on human macrophages derived from cord blood (CB) monocytes. We demonstrate that low-dose metformin promotes expansion of M2 anti-inflammatory macrophages, contrasted with high-dose treatment, which exacerbates inflammation by favoring M1 polarization and restricting M2 phenotype. These findings highlight that metformin hold immunomodulatory ability by regulating macrophage polarization in a dose-dependent manner, and only when applied at low dose, exhibiting potential for beneficial anti-inflammatory adjuvant in BPD setting.

Polarization

Bronchopulmonary dysplasia

Cord blood

Inflammation

Adverse effect

© 2022 Published by Elsevier Inc.