Allergy, asthma & immunology research · 2026
Metformin Promotes Acquisition of Immune Tolerance in Allergen-Specific Immunotherapy.
СтатьяНазвание и аннотация: Перевод в очереди
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Park Yu-Mi, Kim Ji An, Kim Hana, Yoon Jong-Seo, Kim Hyun Hee, Chun Yoon Hong
Аннотация
PURPOSE: Subcutaneous immunotherapy (SCIT) is a safe, effective immunotherapy method. However, it has several limitations, most notably the prolonged build-up phase. Metformin regulates Th17/regulatory T-cell (Treg) homeostasis by increasing Tregs and anti-inflammatory cytokines. To overcome the limitation of the long build-up phase of SCIT, we propose combining SCIT with metformin.
METHODS: Sensitized BALB/c mice received intraperitoneal metformin (100 mg/kg or 300 mg/kg) for 9 days, except for the negative, positive, and SCIT groups. The SCIT, SCIT combined with 100 mg/kg metformin (SCIT-Met(100)), and SCIT combined with 300 mg/kg metformin (SCIT-Met(300)) groups received 3 subcutaneous injections of house dust mite (HDM) extract at 2-day intervals for immunotherapy. All groups except the negative control were given intranasal HDM extract for 5 days. Nasal symptoms, ear swelling, eosinophil count in nasopharyngeal wash-out lavage, antibody levels, and nasal mucosa histopathology were analyzed.
RESULTS: All immunotherapy groups exhibited reduced nasal symptoms, ear swelling, eosinophil counts in nasopharyngeal lavage, eosinophils, mast cells, and goblet cells in the nasal mucosa compared to the positive and metformin-injected (Met) groups. HDM-specific immunoglobulin G1 levels increased in all immunotherapy groups. The SCIT-Met groups induced more Treg than the Met(100), Met(300) and SCIT groups. Interleukin (IL)-4, IL-5 and IL-13 mRNA levels were lower in the Met groups and SCIT-Met(300) group than in the SCIT and SCIT-Met(100) groups. Foxp3 mRNA level was significantly higher in the Met groups and SCIT-Met groups than in the SCIT group.
CONCLUSIONS: Overall, the SCIT-Met(300) group showed relatively favorable outcomes compared with the other groups. Combining immunotherapy with metformin may alleviate allergy symptoms and enhance immune tolerance in a murine model of allergic rhinitis. Further studies are needed to confirm these findings.
METHODS: Sensitized BALB/c mice received intraperitoneal metformin (100 mg/kg or 300 mg/kg) for 9 days, except for the negative, positive, and SCIT groups. The SCIT, SCIT combined with 100 mg/kg metformin (SCIT-Met(100)), and SCIT combined with 300 mg/kg metformin (SCIT-Met(300)) groups received 3 subcutaneous injections of house dust mite (HDM) extract at 2-day intervals for immunotherapy. All groups except the negative control were given intranasal HDM extract for 5 days. Nasal symptoms, ear swelling, eosinophil count in nasopharyngeal wash-out lavage, antibody levels, and nasal mucosa histopathology were analyzed.
RESULTS: All immunotherapy groups exhibited reduced nasal symptoms, ear swelling, eosinophil counts in nasopharyngeal lavage, eosinophils, mast cells, and goblet cells in the nasal mucosa compared to the positive and metformin-injected (Met) groups. HDM-specific immunoglobulin G1 levels increased in all immunotherapy groups. The SCIT-Met groups induced more Treg than the Met(100), Met(300) and SCIT groups. Interleukin (IL)-4, IL-5 and IL-13 mRNA levels were lower in the Met groups and SCIT-Met(300) group than in the SCIT and SCIT-Met(100) groups. Foxp3 mRNA level was significantly higher in the Met groups and SCIT-Met groups than in the SCIT group.
CONCLUSIONS: Overall, the SCIT-Met(300) group showed relatively favorable outcomes compared with the other groups. Combining immunotherapy with metformin may alleviate allergy symptoms and enhance immune tolerance in a murine model of allergic rhinitis. Further studies are needed to confirm these findings.