D2.167 - Effect of Metformin on allergen specific immunotherapy

We present new approach combined AIT with metformin. We aim to compare the differences in immune responses between conventional SCIT and the new approach and to determine whether faster acquisition of immune tolerance was possible.

Mice were sensitized through intraperitoneal injection of Der P extract. Sensitized BALB/c mice were intraperitoneally injected with metformin at 100mg/kg and 300mg/kg, respectively, except for negative, positive and conventional SCIT group (they were intraperitoneally injected with PBS) for 9 consecutive days. And conventional SCIT group, some mice injected 100mg/kg metformin and some mice injected 300mg/kg metformin received three subcutaneous injections with HDM extract (SCIT), but negative group, positive group, the others mice injected 100mg/kg metformin and the others mice injected 300mg/kg metformin received PBS at 2-day intervals for immunotherapy. All except the negative control were administered with HDM extract intranasally for 5 consecutive days. We analyzed for nasal symptoms, ear swelling, eosinophil count, antibody levels, and histopathology of the nasal mucosa. The supernatant from splenocyte culture was analyzed for cytokine production.

All immunotherapy groups (conventional SCIT, and 100 and 300 metformin-injected & SCIT(Met-SCIT) groups) exhibited reduced nasal symptoms, ear swelling, eosinophil count in nasopharyngeal lavage, and the number of eosinophils, mast cells, and goblet cells in the nasal mucosa compared to the positive control and only metformin-injected(MI) groups. The serum levels of HDM-specific IgG1 increased in all immunotherapy groups; however, IgG2a tended to increase more in 300 Met-SCIT group than in the SCIT and 100 Met-SCIT groups. Met-SCIT groups were shown to have a greater ability to induce regulatory T cells than the SCIT group. Interleukin (IL)-4, IL-5, IL-13, IL-17, and IFN-r level were lower in the Met-SCIT groups than in the conventional SCIT group, and decreased as the metformin dose increased. TGF-b and Foxp3 showed a greater increase in the Met-SCIT groups than in the conventional SCIT group.

Overall the 300 Met-SCIT immunotherapy group had similar or better results compared with the conventional SCIT or the 100 Met-SCIT groups. Immunotherapy combined with metformin may reduce allergic symptoms and induced tolerance in a murine model of allergic rhinitis. However, it appears that further evaluation will be needed.