EXPRESSION OF INTERLEUKIN-1-ALPHA, INTERLEUKIN-1-BETA AND INTERLEUKIN-1 RECEPTOR ANTAGONIST MESSENGER-RNA IN MOUSE-BRAIN - REGULATION BY BACTERIAL LIPOPOLYSACCHARIDE (LPS) TREATMENT

Lipopolysaccharide (LPS) stimulation is known to induce interleukin-1 (IL-1) mRNA expression in various immune cell types. Since IL-1 synthesis has been suggested to occur locally in brain tissue, we investigated the expression of IL-1 (alpha and beta) and IL-1 receptor antagonist (IL-1ra) mRNAs in various structures of the central nervous system, as well as in the spleen, following intraperitoneal injection of LPS (100 mu g/mouse). After RNA extraction and amplification by the reverse transcription-polymerase chain reaction (RT-PCR), the PCR products were separated on an agarose gel, transferred and hybridized with digoxigenin-labeled probes synthetized by nested PCR. Glyceraldehyde phosphate deshydrogenase mRNA was used as an internal control. Under basal conditions the expression of IL-1 alpha, IL-1 beta and IL-1ra mRNAs in the brain was extremely low for the three cytokines; in the spleen these mRNAs were clearly detectable. Following LPS stimulation, mRNAs were strongly increased in all the tested tissues (cortex, hippocampus, hypothalamus, cerebellum, pituitary and spleen). The kinetics of mRNAs expressions in the brain were similar for all the tested regions, with a maximum at 6 h and a decrease up to 24 h after LPS administation. In the spleen the maximum was observed as soon as 1 h following stimulation. In conclusion, peripheral LPS stimulation induces a strong and transient expression of IL-1 alpha and IL-1 beta mRNAs in the brain. IL-1ra mRNA is also stimulated by LPS in various regions of the brain. This wide distribution for IL-1 mRNA expression in various brain regions is suggestive of IL-1 synthesis by non-neuronal cells such as glial or endothelial cells. The factors regulating the central expression of these cytokines and the cellular localization of this expression remain to be determined.