科研之友
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摘要
Background: Asthma is thought to result from the generation of T helper type 2 (Th2) responses, leading to bronchial inflammation. IFN-lambda 1 (also known as IL-29) is a recently described member of the IFN-lambda family and has been shown to decrease production of Th2 cytokines in vitro. However, the role and mechanism of IFN-lambda 1 in asthma remain unknown. Objectives: The aim of this study was to clarify the importance of IFN-lambda 1 in allergen-induced airway hyperresponsiveness (AHR) and inflammation. Methods: We used a murine model for ovalbumin (OVA)-induced asthma to examine the effect of intranasal delivery of recombinant adenovirus expressing human IFN-lambda 1 (Ad-hIFN-lambda 1) on AHR and allergic airway inflammation. Results: Intranasal instillation of Ad-hIFN-lambda 1 before airway antigen challenge in OVA-immunized mice significantly decreased the severity of AHR and numbers of eosinophils and levels of IL-4, IL-5, and IL-13, but not IL-10 and IFN-gamma; both in vivo, in the bronchoalveolar lavage fluid and in vitro, following stimulation of lymphocytes from spleens with OVA, compared with administration of a control virus (Ad-mock). Furthermore, Ad-hIFN-lambda 1 treatment inhibited serum IgE secretion and increased numbers of splenic CD4(+)CD25(+)FOXP3(+) Treg cells. Histological studies showed that Ad-hIFN-lambda 1 attenuated OVA-induced lung tissue eosinophilia. Conclusions: These results demonstrate that delivery of the Ad-hIFN-lambda 1 can mitigate allergic airway inflammation in experimental asthma. The potent immunoregulatory action of IFN-lambda 1 may offer a novel therapeutic approach to treat allergic asthma.
