Ozone therapy restores immune dysfunction in refractory idiopathic granulomatous mastitis as a novel potential...

Immunological dysfunction has been suggested to play a major role in the pathogenesis of idiopathic granulomatous mastitis (IGM). We recently showed that ozone therapy was effective in patients with steroid-resistant IGM. This study assessed alterations in intracellular cytokine expression patterns in different T-lymphocyte subsets after ozone therapy in refractory IGM. Peripheral blood T lymphocyte subsets (CD8⁺ , CD4⁺ , CD4⁺ CD25⁺ CD127^- ) were analyzed via flow-cytometry for intracellular cytokine expressions IFN-γ, TNF-α, IL-10, and TGF-β before and after completion of 4-month systemic ozone therapy. Ozone therapy significantly increased the CD4⁺ IFN-γ⁺ (p = 0.032), CD4⁺ TNF-α⁺ (p = 0.028), and the CD8⁺ TNF-α⁺ (p = 0.012) T cells. In contrast, significant decreases in CD4⁺ IL-10⁺ (p = 0.047) and CD8⁺ IL-10⁺ T cells (p = 0.022) and CD4⁺ CD25⁺ CD127^-//low Treg cells secreting TGF-β (p = 0.005) were found after ozone therapy. When patients were analyzed according to the response to ozone therapy, patients with a complete remission were more likely to have increased CD3^- CD16⁺ CD56⁺ natural killer cells (p = 0.0027) and decreased CD19⁺ B lymphocytes (p = 0.046) following ozone therapy. Our results suggest that ozone therapy stimulated a T-helper-1 response associated with IFN-γ production and downregulation of TGF-β expression in CD4⁺ CD25⁺ CD127^- Treg cells. These alterations in the immune system following ozone therapy can improve wound healing and restore immune dysfunction in patients with refractory IGM.