Murine subcutaneous immunotherapy models with beneficial immunological and physiological effects

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.

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

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.

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.

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