ENDOTOXIN-INDUCED APPEARANCE OF IMMUNOREACTIVE INTERLEUKIN-1-BETA IN RAMIFIED MICROGLIA IN RAT-BRAIN - A LIGHT AND ELECTRON-MICROSCOPIC STUDY

Interleukin-1 plays an important role as mediator of endotoxin-induced responses in the brain such as fever, sleep, anorexia, behavioural an d neuroendocrine changes. In the present study, interleukin-1 beta imm unocytochemistry has been performed at the light and electron microsco pic level to study the cellular and subcellular localization of interl eukin-1 beta in the brains of rats given endotoxin or saline. Light mi croscopic analysis of rats killed 4, 8 or 24 h after endotoxin (2.5 mg /kg) given intraperitoneally or intravenously revealed a region-specif ic localization of immunoreactive interleukin-1 beta in macrophages an d microglial cells. After saline treatment, no induction of interleuki n-la immunoreactivity occurred in the brain. After administration of e ndotoxin, many interleukin-1 beta-positive cells were found in the men inges, choroid plexus, circumventricular organs, cerebral cortex and h ypothalamus. The number of interleukin-1 beta-positive microglial cell s reached a maximum 8 h after administration of endotoxin, irrespectiv e of the route of administration. In general, more interleukin-1 beta- positive microglial cells were found after intravenous than after intr aperitoneal administration of endotoxin. Interleukin-1 beta-positive m icroglial cells were often grouped in patches in the vicinity of blood vessels. At the surface of the cerebral cortex, in the meninges, inte rmediate cell forms between interleukin-1 beta-positive macrophages an d microglial cells were found. interleukin-1 beta-positive perivascula r microglia were localized at the brain side of the basal lamina. Immu noreactive interleukin-1 beta was found at the luminal side of the end othelial cells lining the venules. Furthermore, microglial cells that extended their processes into the ependymal layer of the third ventric le were observed. Results of the electron microscopic studies revealed immunoreactive interleukin-1 beta in many cells with the cellular cha racteristics of microglial cells, but also, in some cells, identified as astrocytes. In microglial cells, immunoreactive interleukin-1 beta was found in the cytoplasm but not in the endoplasmatic reticulum or G olgi apparatus. These results show that after peripheral administratio n of endotoxin, immunoreactive interleukin-1 beta is induced in macrop hages in the meninges and in the choroid plexus, as well as in microgl ial cells in parenchyma. Interleukin-1 beta produced by these cells ma y serve as a signal for adjacent or more distant targets (neurons, end othelial cells, microglial cells) to play a role in the induction of n on-specific symptoms of sickness.