Increased expression of mRNA encoding interleukin-1 beta and caspase-1, and the secreted isoform of interleukin-1 receptor antagonist in the rat brain following systemic kainic acid administration

Kainic acid, an analogue of glutamate, injected systemically to rats evokes seizures that are accompanied by nerve cell damage primarily in the limbic system. In the present study, we have analyzed the temporal profile of the expression of the cytokines interleukin-1 beta (IL-1 beta) and IL-1 recept or antagonist (IL-1ra), and the related IL-1 beta-converting enzyme (ICE/ca spase-1), in different regions of the vat brain in response to peripheral k ainic acid administration (10 mg/kg, i.p.). In situ hybridization histochem istry experiments revealed that IL-1 beta mRNA-expressing cells, morphologi cally identified as microglial cells, were mainly localized to regions show ing pronounced neuronal degeneration; hippocampus, thalamus, amygdala, and certain cortical regions. The strongest expression of IL-1 beta mRNA was ob served after 12 hr in these regions. A weak induction of the IL-1 beta mRNA expression was observed already at 2 hr. Similar results were obtained by RT-PCR analysis, showing a significantly increased expression of IL-1 beta mRNA in the hippocampus and amygdala after 12 hr. in addition, RT-PCR analy sis revealed that IL-1ra mRNA, and specifically mRNA encoding the secreted isoform of IL-1ra (sIL-1ra), was strongly induced in the hippocampus and am ygdala at 12 and 24 hr postinjection. RT-PCR analysis of mRNA encoding casp ase-1 showed a significantly increased expression in the amygdala after 12 hr. in conclusion, in response to systemic kainic acid injection IL-1 beta mRNA is rapidly induced and followed by induction of IL-1ra mRNA and caspas e-1 mRNA, supporting a role of the IL-1 system in the inflammatory response during excitotoxic damage. (C) 2000 Wiley-Liss, Inc.