BACTERIAL LIPOPOLYSACCHARIDE-INDUCED EXPRESSION OF INTERLEUKIN-6 MESSENGER-RIBONUCLEIC-ACID IN THE RAT HYPOTHALAMUS, PITUITARY, ADRENAL-GLAND, AND SPLEEN

Whereas the stimulatory effect of interleukin-6 (IL-6) on the hypothal amic-pituitary-adrenal (HPA) axis is well established, its mode of act ion in this axis has yet to be fully elucidated. To further study the role of IL-6 in the HPA axis, we compared the expression of IL-6 messe nger RNA (mRNA) in the rat hypothalamus, pituitary, and adrenal gland with that in the spleen after ip or intracerebroventricular (icv) admi nistration of bacterial lipopolysaccharide (LPS). After either ip or i cv administration, LPS induced the expression of IL-6 mRNA, which cons ists of 1.2 kilobases (kb) and 2.4 kb subclasses, in all these tissues of the HPA axis as well as in the spleen. Although we used 100 times less amount of LPS for the icv administration than that used for ip LP S, plasma ACTH levels in both the conditions rapidly reached comparabl e levels. This icv dose induced IL-6 mRNA expression in the hypothalam us faster than ip dose but also stimulated IL-6 mRNA expression in the hypothalamus, pituitary, and adrenal gland more effectively and smoot hly than the ip LPS dose did. Northern blot analysis revealed that in the hypothalamus, pituitary, and adrenals, the predominant subclass of IL-6 mRNA was not 1.2 kb but 2.4 kb. In contrast, this subclass was t he minor component in the spleen induced under the same circumstances. These findings indicate that IL-6-synthesizing cells in the HPA axis differ in character from those in the spleen, and that LPS applied in vivo may modulate IL-6 expression in these cells directly and/or indir ectly through secondarily activated functions in the neuronal or endoc rine systems.