Interleukin-1β Inhibits Glutamate Release in Hippocampus of Young, But Not Aged, Rats

Abstract

The proinflammatory cytokine, interleukin-1, is synthesized in neuronal and glial cells and is released in response to stress/injury. IL-1 exerts profound effects on the central nervous system, which include an inhibitory effect on synaptic activity in hippocampus, a brain area expressing a high density of IL-1 receptors. We report that IL-1β has an inhibitory effect on KCl-stimulated release of glutamate and KCl-stimulated [ 45Ca] influx in synaptosomes prepared from hippocampus of 4-month-old rats. These effects were inhibited by the endogenous receptor antagonist, IL-1ra, and by the phospholipase A 2 (PLA 2) inhibitor, quinacrine, suggesting that IL-1 receptor activation is coupled to PLA 2. An inhibitory effect of IL-1β on protein kinase C activity was also observed. KCl-induced calcium-dependent release and calcium influx, and protein kinase C activity were significantly decreased in hippocampal synaptosomes prepared from 22-month-old compared to 4-month-old animals. In contrast to the inhibitory effect of IL-1β in synaptosomes prepared from young adult animals, no effect was observed on release, calcium influx, or protein kinase C activity in synaptosomes prepared from aged animals. We report that there is an age-related increase in expression of IL-1β in hippocampus and propose that this change may underlie the attenuated responses to IL-1β in hippocampus of aged animals.