The cytokine interleukin-1beta (IL-1beta) mediates and exacerbates excitotoxic brain damage in the rat striatum. Co-injection of the selective glutamate receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (S-AMPA) with human recombinant IL-1beta (hrIL-1beta) in the striatum of rats results in both local (striatal) damage and extensive, distant neuronal death in the cortex. The objective of the present study was to investigate the mechanisms underlying IL-1beta actions on excitotoxic damage, and to determine whether this effect of IL-1beta, a potent pyrogen, is due to modification of body temperature. Striatal infusion of S-AMPA (7.5 nmol) in anaesthetised rats produced localised striatal damage. Intrastriatal co-infusion of hrIL-1beta (10 ng) with S-AMPA caused similar striatal damage, but also produced extensive cortical damage, together with a modest increase in body temperature (0.9 degrees C) compared to rats infused with S-AMPA alone. Infusion of S-AMPA into the striatum, together with intracerebroventricular (i.c.v.) injection of hrIL-1beta, produced a similar rise in temperature to striatal co-infusion of S-AMPA and hrIL-1beta, but resulted in only local (striatal) neuronal damage, that was similar to that caused by striatal infusion of S-AMPA alone. These data suggest that the effects of IL-1beta on AMPA-receptor mediated neuronal damage in the striatum can be dissociated from its pyrogenic effects on body temperature.
Copyright 1999 Elsevier Science B.V.