Vol. 156, No. 1, 1988 October 14, 1988 BIOCHEMICAL AND BIOPHYSICALRESEARCH COMMUNICATIONS Pages 61-67 IDENTIFICATION OF A HIGH-AFFINITY RECEPTOR FOR INTERLEUKIN-1 BETA IN RAT BRAIN Goro Katsuura, Paul E. Gottschall and Akira Arimura U.S.-Japan Biomedical Research Laboratories, Tulane University Hebert Center, Belle Chasse, LA 70037; and Departments of Medicine and Anatomy, Tulane University School of Medicine, New Orleans, LA 70112 Received August 18, 1988 SUMMARY: A single type of high-affinity binding sites for IL-1 beta was identified in the rat hypothalamus (Kd=l.0 + 0.2 nM) and cerebral cortex (Kd=l.3 +- 0.2 nM), but not in the pituitary. The maximum binding capacity (Bmax) in the hypothalamus (Bmax=75.4 _+ 10.8 fmol/mg protein) was 4 times greater than in the cerebral cortex (Bmax=17,2 + 1.5 fmol/mg protein). Neither various neuropeptides nor IL-2 appeared to influence the binding of [125I]IL-1 beta to the hypothalamic membrane preparations. The potency of unlabeled IL-1 alpha to replace the binding of [125I]IL-1 beta to the hypothalamic membrane preparations was considerably less than that of unlabeled IL-1 beta. These findings indicate that IL-1 beta receptors are heterogeneously distributed in the central nervous system and that IL-1 alpha does not bind with IL-1 beta receotors in the brain ®~9a8Ao~demic Press, zno. The neuroendocrine and immune systems are now recognized as being intimately linked and bidirectionally communicating (1). A prototypical immunotransmitter interleukin- 1 (IL- 1), produced by activated monocytes and macrophages which triggers various immune responses, has been reported as modulating the activities of the endocrine organs and the central nervous system (2-4). IL-1 stimulates adrenocortictropic hormone (ACTH) secretion from the pituitary via corticotropin releasing hormone (CRH) in the hypothalamus (5-7). Furthermore, IL- 1 exerts other central effects such as induction of fever (2), slow-wave sleep (8), satiety (9) and analgesia (10). IL- 1 is synthesized not only in monocytes and phagocytes, but also in astrocytes and glia (11, 12) and can be detected in the cerebrospinal fluid (13). Recent immunohistochemical study has ABBREVIATIONS Interleukin (IL), Adrenocorticotropic hormone (ACTH), Corticotropin releasing hormone (CRH), Growth hormone releasing factor (GRF), Somatostatin-14 (SS-14), Thyrotropin releasing hormone (TRH), Neuropeptide Y (NPY), Neurotensin (NT), Luteinizing hormone releasing hoxmone (LH-RH), Leu-enkephalin (L-Enk), Met-enkephalin (M-Enk), Angiotensin II (A-H), Vasoactive intestinal polypeptide (VIP) 61 0006-291X/88 $1.50 Copyright © 1988 by Academic Press, Inc. All rights of reproduction in any form reserved.