ADRENALECTOMY ENHANCES PRO-INFLAMMATORY CYTOKINES GENE-EXPRESSION, INTHE SPLEEN, PITUITARY AND BRAIN OF MICE IN RESPONSE TO LIPOPOLYSACCHARIDE

To assess the possible influence of endogenous glucocorticoids on cyto kine expression in the brain, adrenalectomized mice and sham operated mice were injected with saline or lipopolysaccharide (LPS, 10 mu g/mou se, subcutaneously) and the levels of transcripts for IL-1 alpha, IL-1 beta, IL-1ra, IL-6 and tumor necrosis factor-alpha (TNF alpha) were d etermined 2 h after treatment in the spleen, pituitary, hypothalamus, hippocampus and striatum, using semi-quantitative reverse transcriptio n polymerase chain reaction (RT-PCR). Levels of IL-1 beta were measure d by ELISA in plasma and tissues of mice sacrificed after the administ ration of LPS or saline. LPS induced the expression of pro-inflammator y cytokines at the mRNA level in all tissues under investigation, exce pt for TNF alpha in the hippocampus. This effect was potentiated by ad renalectomy in the spleen for IL-1 alpha and IL-1ra, the pituitary for cytokines other than IL-1ra, the hypothalamus for all cytokines, the hippocampus for cytokines other than TNF alpha, and the striatum for I L-1 alpha and IL-6. In saline-treated mice, adrenalectomy increased IL -1 alpha and IL-1 beta gene expression in the hypothalamus and IL-1 al pha gene expression in the hippocampus and striatum. LPS increased pla sma and tissue levels of IL-1 beta, as determined by ELISA, and this e ffect was potentiated by adrenalectomy in plasma and tissues other tha n the spleen. These results can be interpreted to suggest that endogen ous glucocorticoids regulate the neural components of the host respons e to infection and inflammation by inhibiting cytokine expression in p eripheral organs and the brain.