Effects of peripheral administration of LPS on the expression of immunoreactive interleukin-1 alpha, beta, and receptor antagonist in rat brain.

The cytokine interleukin-1 (IL-1) appears to play a pivotal role in the orchestration of brain-mediated, nonspecific illness symptoms during an infection. In the present study, we examine the possibility that IL-1 is produced in the central nervous system itself, which may be responsible for the induction of brain-mediated responses. Using immunocytochemical techniques, we demonstrated that peripheral administration of bacterial endotoxin to rats caused a time- (1.5-24 hr) and dose-dependent (4 micrograms/kg-2.5 mg/kg) induction of IL 1 beta immunoreactivity in cells identified as macrophages in meninges and choroid plexus and microglial cells in various brain regions. At 8 hr after endotoxin (2.5 mg/kg), immunoreactive IL-1 alpha was observed in the same areas and cell types as IL-1 beta. Although no quantitative measurements have been performed, it appears that fewer cells express immunoreactive IL-1 alpha than IL-1 beta. Furthermore, IL-1ra was found to be constitutively expressed in neurons in the paraventricular nucleus and supraoptic nucleus, which is in accordance with mRNA data. After administration of endotoxin, we observed no additional cells that expressed immunoreactive IL-1ra. We conclude that IL-1 alpha and IL-1 beta production in the brain is induced in the same cell types, whereas IL-1ra is expressed constitutively by a different cell type--probably neurons.