TYPE-1 INTERLEUKIN-1 RECEPTOR IN THE RAT-BRAIN - DISTRIBUTION, REGULATION, AND RELATIONSHIP TO SITES OF IL-1-INDUCED CELLULAR ACTIVATION

Systemic interleukin-l (IL-1) activates the hypothalamo-pituitary-adre nal (HPA) axis, an effect exerted through increased synthesis and secr etion of corticotropin-releasing factor (CRF) by parvicellular neurose cretory neurons. The site(s) and mechanism(s) through which circulatin g IL-1 may access central systems governing HPA axis output remain obs cure. To identify potential cellular targets for blood-borne IL-1, we analyzed the distribution of mRNA encoding the rat type 1 IL-1 recepto r (IL-1R1) in rat brain. Regional ribonuclease protection assays detec ted a single protected fragment corresponding to the membrane-bound fo rm of the IL-1R1 mRNA in all areas analyzed. In situ hybridization rev ealed labeling predominantly over barrier-related cells, including the leptomeninges, non-tanycytic portions of the ependyma, the choroid pl exus, and vascular endothelium. Low to moderate levels of the IL-1R1 m RNA were detected in just a few neuronal cell groups, including the ba solateral nucleus of the amygdala, the arcuate nucleus of the hypothal amus, the trigeminal and hypoglossal motor nuclei, and the area postre ma. No specific labeling for IL-1R1 mRNA was detected over neurons tha t respond to intravenous IL-1 beta by induction of transcription facto r Fos, including hypophysiotropic CRF cells and brainstem catecholamin e neurons. Injection of IL-1 beta did, however, provoke induction of m RNA encoding the immediate-early gene, NGFI-B, but not c-fos, in two m ajor loci of IL-1R1 expression, vascular endothelial cells, and the ar ea postrema. Intravenous injection of IL-1 beta acutely down-regulated IL-1R1 mRNA in perivascular cells, but not in neuronal cell groups. T hese results suggest the parenchymal sites of IL-1R1 expression in rat to be distinct from those reported previously in mouse. The common ex pression in both species of an IL-1R in non-neuronal elements highligh ts the possibility that IL-l-mediated activation of CRF neurons may re sult from cytokine-receptor interaction at vascular, and/or other barr ier-related, sites to trigger release of secondary signalling molecule s in a position to interact with components of HPA control circuitry. (C) 1995 Wiley-Liss, Inc.