TIME-COURSE AND LOCALIZATION PATTERNS OF INTERLEUKIN-1-BETA MESSENGER-RNA EXPRESSION IN BRAIN AND PITUITARY AFTER PERIPHERAL ADMINISTRATIONOF LIPOPOLYSACCHARIDE

The inflammatory cytokine interleukin-1 has been implicated as a media tor of many centrally controlled responses, such as fever and increase d activity of the hypothalamic-pituitary-adrenal axis, after systemic infections. To identify the neuroanatomical loci of brain interleukin- 1-producing cells during infection, we investigated interleukin-1 beta messenger RNA expression by ill situ hybridization histochemistry usi ng a 500 nt ribonucleotide probe applied on brain sections from rats i njected intraperitoneally with 2.5 mg/kg bacterial lipopolysaccharide or saline. In control animals, interleukin-1 beta messenger RNA was no t detectable. In the brains of lipopolysaccharide-injected animals, tw o temporally and spatially distinct waves of interleukin-1 beta messen ger RNA induction were observed. First, cell labelling appeared at 0.5 h, peaked at 2 h, and declined at 4-8 h. The labelled cells were conc entrated in circumventricular organs organum vasculosum of the lamina terminalis, subfornical organ, median eminence, and area postrema and in choroid plexus, meninges, and blood vessels. Second, at 8-12 h, sca ttered small cells became labelled throughout the entire brain parench yma; the labelling subsided by 24 h. Labelling was not observed in any neurons. In the pituitary, lipopolysaccharide induced strong interleu kin-1 beta messenger RNA expression initially in the anterior lobe at 0.5-1 h, and later in the neural lobe at 1-2 h, and subsiding thereaft er. The results show that at early rime points, peripheral lipopolysac charide induces interleukin-1 beta message production at the blood-bra in barrier and in circumventricular organs where the blood-brain barri er is leaky. After a time delay of 6-10 h, however, interleukin-1 beta messenger RNA is primarily expressed by non-neuronal cells of the bra in in the brain parenchyma. These results suggest that the source of i nitial brain IL-1 activity after peripheral lipopolysaccharide injecti on derives from cells of the blood-brain barrier and the circumventric ular organs, and the sustained interleukin-1 activity in the central n ervous system thereafter is derived from glia . Published by Elsevier Science Ltd.