Introduction:
To explore the mechanism of action of azithromycin on lung oxidative injury and immune function in mice infected with Mycoplasma pneumoniae (MP) based on the nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway.

Material and methods:
The lung index, dry/wet weight ratio, inflammatory factor levels in alveolar lavage fluid, serum contents of interferon-γ (IFN-γ) and immunoglobulin G (IgG), oxidative stress markers, peripheral blood levels of T-lymphocyte subsets, pathological changes, and Nrf2, HO-1, and NQO1 expression were assessed.

Results:
Compared to the control group, the MP group exhibited elevated lung index, reduced lung dry/wet weight ratio, elevated tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 contents, reduced IL-10 levels, raised IFN-γ, IgG and peripheral blood CD8+ levels, reduced CD3⁺ and CD4⁺ levels, CD4⁺/CD8⁺ ratio, and superoxide dismutase (SOD) and glutathione (GSH) activity, elevated malondialdehyde (MDA) contents, destruction of lung tissue structure, elevated pathological scores, and diminished Nrf2, HO-1, and NQO1 levels. Compared with MP and MP + DMSO groups, MP + azithromycin (AZI) and MP + sulforaphane (SFN) groups displayed a reduced lung index, elevated lung dry/wet weight ratio, reduced TNF-α, IL-1β, and IL-6 contents, raised IL-10 content, decreased IFN-γ, IgG, and peripheral blood CD8⁺ levels, increased CD3⁺ and CD4⁺ levels and CD4⁺/CD8⁺ ratio, raised SOD and GSH activity, and diminished MDA content. HE staining demonstrated improved lung tissue structure, diminished pathological scores, and upregulated Nrf2, HO-1, and NQO1 levels after azithromycin and SFN intervention compared to the MP group (all p < 0.05).

Conclusions:
Azithromycin ameliorates MP infection-induced lung injury and oxidative stress and strengthens immune function in mice, which may be achieved by activating the Nrf2/ARE signaling pathway.