Immunohistochemical localization of interleukin-1beta, interleukin-1 receptor antagonist and interleukin-1beta converting enzyme/caspase-1 in the rat brain after peripheral administration of kainic acid.

The temporal and anatomical distribution of members of the interleukin-1 system in the rat brain following intraperitoneal kainic acid administration was studied in relation to neurodegeneration as detected with in situ end labelling. Kainic acid administration (10 mg/kg, i.p.) resulted in the induced expression of interleukin-1beta, interleukin- receptor antagonist and caspase-1p10 immunoreactivity in areas known to display neuronal and tissue damage upon excitotoxic lesions. The induction of these proteins was transient. Interleukin-1 immunoreactivity appeared at 5 h, and the interleukin-1 receptor antagonist-immunoreactive cells were first detected at 12 h, whereas the induction of caspase- 1p10 expression was first detected 24 h after kainic acid injection. Double labelling with the microglial marker Ox42 confirmed that both interleukin-1beta and interleukin-1 receptor antagonist were mainly localized in microglial cells. The regional distribution of in situ end-labelled neurons was similar to the distribution of cells expressing interleukin-1beta and interleukin-1 receptor antagonist, whereas the distribution of caspase-1 was more limited. The in situ end-labelled neurons, were, similarly to the interleukin-1beta-positive cells, first detected at 5 h, which is earlier than the induction of caspase-1. Our results show that the induction of IL-1beta and IL-1 receptor antagonist proteins after kainic acid are closely associated with the temporal as well as the anatomical distribution of in situ end-labelled neurons, whereas the induction of caspase-1 protein exhibited a delayed temporal profile and limited distribution. Since cytokine production occurs in activated microglial cells, the inflammatory component seems to be a strong mediator of this type of excitotoxic damage. The late onset of the caspase-1 expression would seem to indicate that this enzyme has no fundamental role in directly causing neuronal cell death induced by systemic kainic acid.