Following viral entry into cells, type-I IFN synthesis and the induction of an anti-viral state within the cell follows a biphasic time course as shown in Figure S1 in File S1. Early synthesis of IFNa and IFNb is followed by engagement of their common receptor, leading to a positive feedback loop that amplifies further synthesis of IFNa and IFNb. Because the majority of our outcomes were measured at 24 h, it is uncertain whether the altered responses to HRV seen in asthma can be attributed to early events after viral detection, or are related to a failure of the IFN-driven positive feedback loop. Responsiveness to IFNb and IFNAR expression appear similar in asthmatic and healthy Cefpiramide sodium donors, so we propose that very early events in the response to HRV may be critical in asthma; this may involve the subtle increases in gene expression noted at the early time points, or the function of existing proteins. It is clear that examining these in some detail should be a focus of future research. There are a number of potential limitations of this study that warrant comment. Firstly, while patients withheld medication for 24 hours prior to blood collection and the doses employed were unlikely to lead to systemic absorption, approximately half the asthma patients were being treated with inhaled corticosteroids. However, we observed similar deficiencies in innate immune function between those asthmatics taking inhaled corticosteroids and those who were not, so we do not think that medication use adequately explains the findings outlined in Figures 1 and 2. Secondly, we studied HRV16, a relatively ��benign�� laboratory-adapted strain of the virus and different findings may be obtained with more virulent HRV strains. Thirdly, the methodologies currently available to investigate innate immune response signalling molecules have several limitations, meaning that key endpoints, such as protein phosphorylation, could not be reliably assessed. Finally, our current experiments examined atopic asthmatics, and our findings, in combination with other recent studies, Dithranol suggest that comparison with non-atopic asthmatics could yield interesting findings.