Immunohistochemical localization of interleukin-1 beta, interleukin-1 receptor antagonist and interleuktn-1 beta 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 sy stem in the rat brain following intraperitoneal kainic acid administration was studied in relation to neurodegeneration as detected with in situ end l abelling. Kainic acid administration (10 mg/kg, i.p.) resulted in the induc ed 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 trans ient. Interleukin-1 immunoreactivity appeared at 5 h, and the interleukin-l receptor antagonist,-immunoreactive cells were first detected at 12 h, whe reas the induction of caspase-1p10 expression was first detected 24 h after kainic acid injection. Double labelling with the microglial marker Ox42 co nfirmed 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 i nterleukin-lp and interleukin-l receptor antagonist, whereas the distributi on of caspase-1 was more limited. The in situ end-labelled neurons, were, s imilarly to the interleukin-l P-positive cells, first detected at 5 h, whic h is earlier than the induction of caspase-1. Our results show that the induction of IL-1 beta and IL-1 receptor antagoni st proteins after kainic acid are closely associated with the temporal as w ell as the anatomical distribution of in situ end-labelled neurons, whereas the induction of caspase-1 protein exhibited a delayed temporal profile an d limited distribution. Since cytokine production occurs in activated micro glial cells, the inflammatory component seems to be a strong mediator of th is type of excitotoxic damage. The late onset of the caspase-1 expression w ould 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.