DIFFERENTIAL PATTERN OF C-FOS MESSENGER-RNA RAT-BRAIN FOLLOWING CENTRAL AND SYSTEMIC ADMINISTRATION OF INTERLEUKIN-1-BETA - IMPLICATIONS FOR MECHANISM OF ACTION

Interleukin-1-beta (IL-1 beta) is a potent activator of the hypothalam ic-pituitary-adrenal (HPA) axis, resulting in the release of corticost eroids from the adrenal glands. This effect is evident after both cent ral and peripheral administration, and controversy surrounds the mecha nism(s) by which systemic administration of this peptide, which should not cross the blood-brain barrier, may activate the HPA axis. In the present study, IL-1 beta was administered systemically (5 mu g/kg i.p. ) or centrally (100 ng i.c.v.) to male rats. Both routes of administra tion of IL-1 beta resulted in significant and comparable activation of the HPA axis, as assessed by analysis of plasma conrticosterone. In a ddition, both routes of administration of IL-1 beta resulted in c-fos mRNA induction in specific regions, as determined by in situ hybridiza tion. These included the meninges, cerebral vasculature, choroid plexu s and circumventricular organs. Semiquantitative analysis revealed tha t both routes of administration resulted in significant and comparable induction of c-fos mRNA in the paraventricular nucleus of the hypotha lamus, as compared with control animals. In contrast, in the nucleus t ractus solitarius (NTS) and central nucleus of the amygdala (CeA), lev els of c-fos mRNA were 3-4 times higher in animals treated intraperito neally compared with intracerebroventricularly. A similar differential activation of c-fos mRNA was observed in the lateral divisions of the parabrachial nucleus (PEN) and bed nucleus of the stria terminalis (B NST). These data indicate that following systemic administration, IL-1 beta may activate specific brain areas through mechanisms distinct fr om those involved following central administration. The differential m agnitude of the c-fos mRNA response in the NTS, PEN, CeA and BNST is c onsistent with vagal activation. Physiologically, these results sugges t that IL-1 beta may have differential central effects depending on it s source or point of entry to the brain.