CENTRAL ENDOTOXIN INDUCES DIFFERENT PATTERNS OF INTERLEUKIN (IL)-1-BETA AND IL-6 MESSENGER-RIBONUCLEIC-ACID EXPRESSION AND IL-6 SECRETION IN THE BRAIN AND PERIPHERY

Centrally injected endotoxin induces high levels of interleukin (IL)-6 in serum, but the mechanisms of this induction and the signal conveyi ng the information from the brain to the periphery are not yet known. To help characterize the pathway of centrally mediated induction of IL -6 in periphery, the cytokine levels were measured in rat serum and ce rebrospinal fluid at different times after intracerebroventricular end otoxin (LPS, 2.5 mu g/rat). In the same experiments, IL-6 and IL-1 bet a messenger RNA (mRNA) expression, measured by Northern blot analysis, were evaluated in the periphery (adrenals, lymph nodes, and mononucle ar cells) and brain (hypothalamus, hippocampus and striatum). In serum , IL-6 levels were highest after 2 h; then they rapidly decreased. IL- 6 mRNA showed the same time-course in adrenals and lymph nodes. The pa ttern in the central nervous system was different: in the cerebrospina l fluid, IL-6 was detectable starting from 2 h, reaching a plateaux at 4-8 h and remaining detectable until 16 h. IL-6 mRNA expression in th e brain areas showed a similar time-course, reaching a maximum at 4-8 h. IL-1 beta mRNA induction started at the same time in brain and peri phery, i.e. 1 h after LPS, but the maximal effect was reached at 2 h i n mononuclear cells, adrenals, and lymph nodes, and at 8 h in brain re gions. The results indicate that circulating IL-6 induced by central L PS is produced mainly peripherally and that synthesis of IL-6 and IL-1 beta are regulated differently in the brain and periphery.