REGULATION OF INTERLEUKIN-6 GENE-EXPRESSION IN RAT

The effects of ip endotoxin administration on interleukin 6 (IL6) transcripts in brain and in peripheral tissues of rats were studied together with the effects of this treatment on IL6 and corticosterone concentrations in blood serum. Northern blot analyses showed a rapid increase of IL6 transcripts in spleen, pituitary gland, and adrenals that was paralleled by pronounced elevations in serum IL6 and corticosterone levels. Adrenalectomy further enhanced the induction of IL6 messenger RNA (mRNA) in spleen and pituitary gland and augmented the increase in serum IL6 bioactivity after lipopolysaccharide (LPS) injection. Corticosterone pretreatment (10 mg/kg) completely blocked the increase of IL6 in serum and IL6 mRNA in spleen, adrenals, and hypophysis. In several brain areas, low amounts of IL6 mRNA were detected under basal, noninflammatory conditions, but in response to LPS there was no change in the IL6 mRNA in hippocampus, hypothalamus, and cerebellum. Neither adrenalectomy nor peripheral injections of sublethal LPS doses of up to 10 mg/kg were capable of increasing IL6 mRNA in the hippocampus. The data do not support the hypothesis that central IL6 biosynthesis via transcription of the gene contributes to the endotoxin-mediated activation of the hypothalamic-pituitary-adrenal system. The results, however, clearly demonstrate that LPS-induced IL6 gene expression is subject to glucocorticoid suppression in peripheral tissues.