In addition, we found CCL5/RANTES to be over-expressed in both nonresponders and relapsers to IFN therapy. CCL5 is a chemokine produced by monocyte/macrophage subsets in the liver, which contributes to recruiting T cells and other leukocytes to the infection site and also to the progression and resolution of liver fibrosis. A recent study from our group suggests that infected hepatocytes represent a cellular source for CCL5 production at early phase of HCV infection, through TLR3mediated sensing of HCV dsRNA intermediates and subsequent activation of NF-kB, a transcription factor pivotal for RANTES synthesis. CCL5 is associated with a Th1 lymphocyte-related cytokine/chemokine profile and HCV clearance. However, CCL5 may also shape the IFN response in the liver by altering the infiltration and activation of hepatic stellate cells, which maintains chronic HCV infection in the liver in part by inhibiting liver fibrosis. Exactly how pre-activated intrahepatic RANTES expression affects IFN responsiveness will require Reversine further study. Our study also presents a predictive model for IFN responsiveness based on a small number of signature genes. Although variants of the IL28B/IFNl3 gene have recently been found to be highly predictive of the response to IFN/ribavirin in HCVinfected patients. Clearly, intrahepatic type III IFN levels of hepatitis C patients are not affected by IL28B polymorphism, nor is it the case in primary hepatocyte cultures infected by HCV in vitro. Thus, the underlying mechanism for differential response in HCV-infected patients remains largely unknown. In our study we show that the expression of RSAD2, IFI6, IFI16, STAT1, CCL5, and XAF1 was highly predictive of the eventual IFN responsiveness to IFN/ribavirin therapy. Future studies will elucidate why lower expression of STAT1 and XAF1 were predictive of IFN responsiveness while expression of RSAD2, IFI6, IFI16, and CCL5 were associated with a poorer response to therapy. The model must also be validated with external data, and though our model had high specificity, further refinement is needed to improve model sensitivity. The assessment of airway responsiveness to methacholine is one of the key tests for diagnosing asthma. Airways naturally respond to stimuli such as methacholine by constricting, resulting in decreased airflow to the lungs. In asthmatic patients, this response occurs more quickly and forcefully, and at lower doses of the airway constricting agent. This heightened response is known as airway hyperresponsiveness.