Recently, T cell cytokines such as IL-17 and IFN-gamma have been shown to play important roles in the progression of brain injury induced by ischemia We have shown that IL-23 from infiltrated macrophages activates gamma delta T cells, thereby inducing IL-17 from these cells However, deletion of the IL-23 gene in mice showed a more dramatic protective effect against brain ischemia reperfusion (I/R) model than gamma delta T cell depletion did, suggesting that IL-23 plays some other pivotal role in brain injury in addition to its role in IL-17 induction To develop therapeutic methods based on these findings, we examined the effect of the JAK kinase inhibitor CP-690550 and an anti-IL12/23 monoclonal antibody on an I/R model CP-690550 efficiently inhibited IL-17 production from memory T cells in vitro and partly suppressed infarct volume increase after I/R Anti-p40 antibody, which blocks both IL-12 and IL-23, efficiently suppressed I/R injury and improved recovery of neurological deficits The number of IL-17-producing cells was decreased by anti-p40 antibody treatment Thus the JAR inhibitor and anti-p40 antibody, both of which have already been under trial for the treatment of several human inflammatory diseases, appear to be promising therapeutic agents for the amelioration of stroke (C) 2010 Elsevier Inc All rights reserved