Inhaled delivery of recombinant interferon-lambda restores allergic inflammation after development of asthma by controlling Th2-and Th17-cell-mediated immune responses

Remarkable progress has recently been achieved to identify the biological function and potential value of novel therapeutic targets for the effective control of allergic asthma. Interferon (IFN)-lambda has been suggested to restrict chronic inflammation in the lungs of asthmatic mice and we sought to determine the contribution of IFN-lambda as an asthma therapeutic. We show that inhaled IFN-lambda can restrict Th2 and Th17 inflammation in the lungs of asthmatic mice, accompanied with alteration of IL-10 secretion. BALB/C mice were used for an asthmatic mouse model with OVA. Recombinant IFN-lambda s (IFN-lambda(2): 2 mu g, IFN-lambda(3): 2 mu g) were inoculated into asthmatic mice after OVA challenge by intranasal delivery. Lungs of asthmatic mice were severely inflamed, with extensive inflammatory cell infiltration and increased goblet cell metaplasia with higher total lung resistance. Transcription of IL-4, IL-5, IL-13, and IL-17A was significantly higher until five days after the final OVA challenge. Asthmatic mice were administered recombinant IFN-lambda via inhalation three times after the last challenge and the asthmatic mice showed improvement in lung histopathologic findings, and total lung resistance was maintained under normal range. IFN-lambda inhalation exhibited significant decreases in Th2 and Th17 cytokine levels, and the populations of Th2 and Th17 cells were recovered from the lungs of asthmatic mice. Additionally, increase in IL-10 secretion from CD4 + Th cells population was observed in response to inhaled delivery of IFN-lambda along with alterations in Th2 and Th17 cell-derived inflammation. Our findings show that inhaled delivery of IFN-lambda can restrict airway inflammation in the lungs of asthmatic mice by controlling Th2-and Th17-mediated responses accompanied by regulation of IL-10 secretion even after asthma development.