Process of pulmonary eosinophilia induced by intratracheal administration of Interleukin-33

Background and objective: IL-33 is a functional cytokine to enhance the activity of eosinophils and to promote their differentiation. We previously demonstrated that significant increase of IL-33 level in bronchoalveolar lavage fluid (BALF) in the initial phase of acute eosinophilic pneumonia in contrast to chronic eosinophilic pneumonia. From our data, it is speculated that IL-33 plays an important role in the acute induction of eosinophila in lung. Therefore, we investigated the sequential process of eosinophilia by local IL-33 treatment. Methods: Recombinant IL-33 protein (5μg/mouse) was directly administered into trachea of BALB/c mice. Sequentially, blood and BALF were obtained up to 10 days after the treatment, and examined the cell numbers, the concentration of IL-5 and albumin. Histological change was also evaluated. Results: Only once IL-33 administration induced prominent pulmonary eosinophilia, and the maximum number of eosinophils in BALF was observed at day 7-10 after the treatment. The concentration of IL-5 of BALF was increased at day 3 and that of albumin attained the peak at day10. Histologically, the accumulation of eosinophis was observed during day 3-10. However, the peripheral blood showed no increase of eosionophils and IL-5. Conclusion: Local administration of IL-33 induced local eosinophilia in lung, without the increase of eosinophils in peripheral blood. In addition, IL-33 induced local IL-5 production and the albumin leakage due to the increase of permeability. Furthermore, it is speculated that the progenitors of eosinophils in lung are able to respond to IL-33 and IL-5, and local proliferation of eosinophils would participate in eosinophilic lung disease.