Mechanisms that underlie these changes in circulating factors are starting to emerge. Alcohol-induced alterations in gene expression involved in cytokine signaling pathways were examined in male and female subjects with alcohol dependence (AD; more than 25 drinks/week prior to study; n=10), heavy drinkers (HD; defined as regular alcohol use over the past year of at least 8 drinks/week for women and at least 15 drinks/week for me; n=13), and moderate drinkers (MD; defined as up to 7 drinks/week for women and 14 drinks/week for men; n=17). After normalization, 436 differentially expressed genes in blood samples were identified: 291 genes differed between AD and MD subjects, 240 between AD and HD subjects, but only 6 differed between HD and MD subjects (Beech, Qu et al. 2012). Many of the differentially expressed genes were involved in the regulation of the immune response by cytokine signaling and the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway. Expression of interferon receptor 2 (IFNAR2) was down-regulated in HD subjects compared to MD subjects which could contribute to deficits in both innate and adaptive immunity