AbstractAn Increasing body of evidence supports a critical role of brain inflammation in the pathogenesis of Alzheimer’s disease. A principal aspect of the brain immune response to inflammation is the activation of microglia. It has been shown that the kinin system is activated during brain inflammation and previously we demonstrated that bradykinin B1receptor agonist reduced microglial activationin vitro. The aim of the present study was to investigate the effects of bradykinin B1or B2receptor antagonists on microglial release of pro-inflammatory factors in BV2 microglia.In vivo, we focused on the effects of intranasally given kinin antagonists on amyloid burden and microglia/macrophage marker expression in brains of 5X familial Alzheimer’s disease mice. The present data show that pharmacological antagonism of B1receptor (R-715) but not B2receptor (HOE-140) markedly increased nitric oxide and tumor necrosis factor alpha release from BV2 microglial cells. We also showed that intranasal treatment with R-715 but not HOE-140 of Alzheimer’s mice enhanced amyloid beta burden and microglia/macrophages activation. Taken together, our data reveal a possible role for the bradykinin B1receptor in neuroinflammation and in the control of Abeta accumulation in transgenic mice, possibly through regulation of glial cell responses.