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 synthe sis has been suggested to occur locally in brain tissue, we investigat ed the expression of IL-1 (alpha and beta) and IL-1 receptor antagonis t (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 we re separated on an agarose gel, transferred and hybridized with digoxi genin-labeled probes synthetized by nested PCR. Glyceraldehyde phospha te deshydrogenase mRNA was used as an internal control. Under basal co nditions the expression of IL-1 alpha, IL-1 beta and IL-1ra mRNAs in t he brain was extremely low for the three cytokines; in the spleen thes e mRNAs were clearly detectable. Following LPS stimulation, mRNAs were strongly increased in all the tested tissues (cortex, hippocampus, hy pothalamus, cerebellum, pituitary and spleen). The kinetics of mRNAs e xpressions 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 stimulat ion. In conclusion, peripheral LPS stimulation induces a strong and tr ansient 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. Th is wide distribution for IL-1 mRNA expression in various brain regions is suggestive of IL-1 synthesis by non-neuronal cells such as glial o r endothelial cells. The factors regulating the central expression of these cytokines and the cellular localization of this expression remai n to be determined.