Immunohistochemical localization of interleukin-1β, interleukin-1 receptor antagonist and interleuktn-1β 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-1 beta, interleukin-l 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-l 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-lp and interleukin-l 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-lp and interleukin-l receptor antagonist, whereas the distribution of caspase-1 was more limited. The in situ end-labelled neurons, were, similarly to the interleukin-l P-positive cells, first detected at 5 h, which is earlier than the induction of caspase-1. Our results show that the induction of IL-1 beta 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. (C) 1999 IBRO. Published by Elsevier Science Ltd.