Immunomodulatory effects of etanercept in a model of brain injury act through attenuation of the acute‐phase response

• DOI: 10.1111/j.1471-4159.2007.04928.x
• Publication Date: 2007-09-22T06:10:42Z
• Authors: Sandra J. Campbell; Yanyan Jiang; Andrew E. M. Davis; Rebecca Farrands; Joanna Holbrook; David Leppert; Daniel C. Anthony
• Keywords: Alpha (finance)

Abstract TNF‐α has proved to be a successful target in the treatment of many peripheral inflammatory diseases, but same interventions worsen immune‐mediated CNS disease. However, anti‐TNF‐α strategies may offer promise as therapy for non‐immune injury. In this study, we have microinjected IL‐1β or lipopolysaccharide (LPS) into rat brain simple model injury and systemically administered antagonist etanercept discover whether hepatic TNF‐α, produced part acute‐phase response injury, modulates brain. We report significant reduction neutrophil numbers recruited IL‐1β‐ LPS‐challenged result inhibition. also show an attenuation levels mRNA including TNF‐α‐induced genes, such chemokines CCL‐2, CXCL‐5, CXCL‐10, although other elevated by were not significantly changed. The chemokine synthesis results reduced circulating neutrophils, liver consequence These findings suggest that inhibitors reduce responses targeting response, thus therapies need cross blood–brain barrier effective.