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

Abstract

Administration of low doses of lipopolysaccharide (LPS) that do not disrupt the blood-brain barrier (BBB) results in the expression of interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF alpha) in the hypothalamus 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 maintenance. 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 superantigen staphylococcal enterotoxin B (SEB), which stimulates T cells by binding to appropriate V beta domains of the T-cell receptor, did not result in induction of IL-1 beta, IL-6, and TNF alpha 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 administration 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 necessary step in the stimulation of the HPA axis by SEB.