Centrally injected endotoxin induces high levels of interleukin (IL)-6 in serum, but the mechanisms of this induction and the signal conveying 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 cerebrospinal fluid at different times after intracerebroventricular endotoxin (LPS, 2.5 μg/rat). In the same experiments, IL-6 and IL-1β messenger RNA (mRNA) expression, measured by Northern blot analysis, were evaluated in the periphery (adrenals, lymph nodes, and mononuclear 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 pattern in the central nervous system was different: in the cerebrospinal fluid, IL-6 was detectable staring from 2 h, reaching a plateaux at 4-8 h and remaining detectable until 16 h. IL-6 mRNA expression in the brain areas showed a similar time-course, reaching a maximum at 4-8 h. IL-1β mRNA induction started at the same time in brain and periphery, i.e. 1 h after LPS, but the maximal effect was reached at 2 h in mononuclear cells, adrenals, and lymph nodes, and at 8 h in brain regions. The results indicate that circulating IL-6 induced by central LPS is produced mainly peripherally and that synthesis of IL-6 and IL-1β are regulated differently in the brain and periphery.
|Number of pages||6|
|Publication status||Published - 1995|
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism