Murine subcutaneous immunotherapy models with beneficial immunological and physiological effects.

Background: Immunotherapy was introduced 100 years ago and has a unique role in the treatment of allergic diseases in that only immunotherapy can induce long-term immunological tolerance. However, only a few mouse models of immunotherapy have been developed so far.

Objective: We tried to establish murine immunotherapy models that have similar findings in human using subcutaneous rush immunotherapy-like schedule.

Methods: To determine the maximal safe or maximal tolerable dose, injection dose was doubled twice a day from the dose of sensitization. Mice with established asthma using ovalbumin (OVA) were repeatedly injected with OVA from the dose of sensitization subcutaneously twice a day: after reaching to the maximal safe or maximal tolerable dose, mice were injected with each dose either 10 times or 24 times.

Results: Short term immunotherapy (10 times) with the maximal safe and tolerable dose of OVA showed decreased IL-5 production, decreased IL-5/INF-γ ratio, and increased IgG2a/IgG1 but there was no significant difference in airway hyperresponsiveness (AHR) or airway inflammation. Prolonged immunotherapy (24 times) with the maximal tolerable dose not only decreased cytokine productions of IL-5 and even INF-γ, but also decreased IgE, IgG1 and even IgG2a production. Remarkably, the prolonged immunotherapy provided a protective effect on AHR.

Conclusion: This study suggested immunotherapy models with some beneficial immunological and physiological effects in murine asthma.