Interleukin-1beta potentiates neuronal injury in a variety of injury models involving energy deprivation.

Abstract

The purpose of this study was to develop a suitable in vitro model system to study the biochemical pathway(s) by which interleukin-1beta (IL-1beta) contributes to the pathogenesis of cerebral ischemia. Thus, the effect of IL-1beta on a number of injury paradigms associated with energy deprivation was investigated using murine mixed cortical cell cultures. While IL-1beta by itself was not neurotoxic, pre-treatment-but not concurrent or post-treatment-with this cytokine potentiated neuronal injury induced by depriving cultures of either oxygen, glucose, or both oxygen and glucose. Cytotoxicity was abolished by an IL-1beta-neutralizing antibody. Together, these results demonstrate the establishment of reliable and reproducible in vitro models that will now allow detailed investigation of the cellular and molecular mechanisms relating to IL-1beta-mediated neuronal cell death.