Not All Peripheral Immune Stimuli That Activate the HPA Axis Induce Proinflammatory Cytokine Gene Expression in the Hypothalamus

ADRIANA DEL REY; ANKE RANDOLF; F.J. PITOSSI; HEINER ROGAUSCH; HUGO BESEDOVSKY

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES.

BLACKWELL PUBLISHING

Lugar: Oxford; Año: 2000 vol. 917 p. 169 - 174

0077-8923

Administration of low doses of lipopolysaccharide (LPS) that do not disrupt the blood–brain barrier (BBB) results in the expression of interleu- kin-113 (IL-113), IL-6, and tumor necrosis factor-alpha (TNFa) in the hypothal- amus in parallel to stimulation of the hypothalamus–pituitary–adrenal (HPA) axis. This endocrine response is triggered by peripheral cytokines, and we recently obtained evidence that brain-borne IL-1 contributes to its mainte- nance. LPS preferentially stimulates cells of the macrophage lineage and B lymphocytes. The possibility that primarily stimulation of other types of peripheral immune cells also results in the expression of proinflammatory cytokines in the brain and in the activation of the HPA axis was investigated. Our results showed that, in contrast to LPS, administration of the superanti- gen staphylococcal enterotoxin B (SEB), which stimulatesT cells by binding to appropriate V13 domains of the T-cell receptor,did not result in induction of IL-113, IL-6, and TNFa expression in the hypothalamus. Furthermore, although IL-2 transcripts in the spleen were highly increased, expression of this gene was not detected in the brain. However, as with LPS, SEB adminis- tration also results in elevated levels of glucocorticoids in blood. Therefore, our data suggest that increased expression of proinflammatory cytokines in the brain is not a necessarystep in the stimulation of the HPA axis by SEB.