INTERLEUKIN-1-BETA AND THE INTERLEUKIN-1 RECEPTOR ANTAGONIST ACT IN THE STRIATUM TO MODIFY EXCITOTOXIC BRAIN-DAMAGE IN THE RAT

The cytokine interleukin-1 (IL-1) has been implicated in ischaemic, tr aumatic and excitotoxic brain damage. The results presented here revea l novel actions of IL-1 in the striatum which markedly exacerbate cort ical neuronal damage elicited by local excitotoxins in the striatum or cortex. Intrastriatal infusion of IL-1 receptor antagonist, IL-1ra, m arkedly inhibited striatal neuronal damage caused by N-methyl-D-aspart ate (NMDA) or pha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA ) receptor activation in the rat. In contrast, intracortical infusion of IL-1ra failed to inhibit NMDA or AMPA receptor-induced damage in th e cortex. Intrastriatal co-infusion of IL-1 beta with the NMDA or AMPA receptor agonist did not affect local striatal damage induced by acti vation of either glutamate receptor subtype, but caused extensive cort ical damage when administered into the striatum with AMPA. This second ary damage was significantly reduced by pretreatment with the NMDA rec eptor antagonist (MK-801), which did not affect local (striatal) damag e caused by AMPA. Infusion of IL-1 beta into the striatum (but not the cortex) markedly enhanced cortical damage caused by infusion of an NM DA or AMPA receptor agonist into the cortex. These data reveal selecti ve actions of IL-1 and IL-1ra in the striatum, which influence cortica l neuronal loss and suggest that IL-1 selectively enhances damage caus ed by AMPA receptor activation.