Neuroprotective actions of endogenous interleukin-1 receptor antagonist (IL-1ra) are mediated by glia

✍ Scribed by Emmanuel Pinteaux; Nancy J. Rothwell; Herve Boutin

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 185 KB
• Volume: 53
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/glia.20308

✦ Synopsis

Abstract

The pro‐inflammatory cytokine interleukin‐1 (IL‐1), contributes to neuronal inflammation and cell death induced by ischemia, excitotoxicity, or trauma, while administration of IL‐1 receptor antagonist (IL‐1ra) reduces neuronal injury. The aim of the present study was to test the hypothesis that endogenous IL‐1ra is neuroprotective in vivo and in vitro, and to identify its mechanism of actions. Mice lacking IL‐1ra (IL‐1ra knock‐out (KO]) exhibited a dramatic increase in neuronal injury (3.6‐fold increase in infarct size) induced by transient cerebral ischemia compared to wild‐type (WT) animals. Basal cell death of cultured cortical neurons from WT and IL‐1ra KO was identical, and treatment with NMDA or AMPA (20 μM) increased cell death to the same extent in WT and IL‐1ra KO neurons. However, basal and NMDA‐ or AMPA‐induced cells death was significantly higher in glial–neuronal co‐cultures from IL‐1ra KO than from WT mice. We further showed that pure microglial cultures, but not pure astrocytes cultures, released IL‐1ra in response to treatment with conditioned medium from NMDA‐ or AMPA‐treated primary neurons. These results demonstrate that endogenous IL‐1ra produced by microglia is neuroprotective in cerebral ischemia or excitotoxicity. © 2005 Wiley‐Liss, Inc.