Acute asthma exacerbations are frequently associated with respiratory viral infections. Although impaired production of type III IFNs (IFN-lambda s) is related to the severity of asthma exacerbation, the mechanisms underlying deficient IFN-lambda production in asthma are poorly understood. Airway epithelial cells were stimulated in vitro with a synthetic mimetic of viral double-stranded RNA (dsRNA). IL-13, a crucial cytokine responsible for asthma pathogenesis, suppressed dsRNA-induced expression of IFN-lambda s, and JAK inhibitor AG490 prevented the suppression by IL-13. IL-13 per se did not affect IFN-lambda production or the expressions of membrane dsRNA receptor TLR3 and of cytoplasmic receptors RIG-I and MDA5. IL-13-deficient mice exhibited more enhanced IFN-lambda expression after intratracheal instillation of dsRNA than wildtype mice, whereas IFN-lambda expression after dsRNA was absent in the mouse lungs of the OVA-induced asthma model. These findings suggest that IL-13 may be a putative cytokine suppressing IFN-lambda production against airway viral infections in asthmatics. (C) 2010 Elsevier Inc. All rights reserved.