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

Cabioglu N., Cetin Aktas E., Emiroglu S., Tukenmez M., Ozkurt E., Muslumanoglu M., ...More

Cell Biology International, vol.47, no.1, pp.228-237, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 47 Issue: 1
  • Publication Date: 2023
  • Doi Number: 10.1002/cbin.11953
  • Journal Name: Cell Biology International
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.228-237
  • Keywords: idiopathic granulomatous mastitis, IFN-gamma, IL-10, ozone therapy, TGF-beta, TNF-alpha
  • Istanbul Medipol University Affiliated: Yes


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.