Adrenalectomy enhances pro-inflammatory cytokines gene expression, in the spleen, pituitary and brain of mice in response to lipopolysaccharide

To assess the possible influence of endogenous glucocorticoids on cytokine expression in the brain, adrenalectomized mice and sham operated mice were injected with saline or lipopolysaccharide (LPS, 10 μg/mouse, subcutaneously) and the levels of transcripts for IL-1α, IL-1β, IL-1ra, IL-6 and tumor necrosis factor-α (TNFα) were determined 2 h after treatment in the spleen, pituitary, hypothalamus, hippocampus and striatum, using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Levels of IL-1β were measured by ELISA in plasma and tissues of mice sacrificed after the administration of LPS or saline. LPS induced the expression of pro-inflammatory cytokines at the mRNA level in all tissues under investigation, except for TNFα in the hippocampus. This effect was potentiated by adrenalectomy in the spleen for IL-1α and IL-1ra, the pituitary for cytokines other than IL-1ra, the hypothalamus for all cytokines, the hippocampus for cytokines other than TNFα, and the striatum for IL-1α and IL-6. In saline-treated mice, adrenalectomy increased IL-1α and IL-1β gene expression in the hypothalamus and IL-1α gene expression in the hippocampus and striatum. LPS increased plasma and tissue levels of IL-1β, as determined by ELISA, and this effect was potentiated by adrenalectomy in plasma and tissues other than the spleen. These results can be interpreted to suggest that endogenous glucocorticoids regulate the neural components of the host response to infection and inflammation by inhibiting cytokine expression in peripheral organs and the brain.