IN-VIVO REGULATION OF THE IL-1-BETA SYSTEM (LIGAND, RECEPTOR-I AND RECEPTOR-II, RECEPTOR ACCESSORY PROTEIN, AND RECEPTOR ANTAGONIST) AND TNF-ALPHA MESSENGER-RNAS IN SPECIFIC BRAIN-REGIONS

Interleukin-1 beta (IL-1 beta) acts directly in the central nervous sy stem (CNS). Here, using a novel behavioral-molecular approach, we repo rt the regulation of the complete IL-1 beta system (ligand, receptors, receptor accessory protein, and receptor antagonist) and TNF-alpha mR NAs in the CNS in response to the chronic intracerebroventricular micr oinfusion of IL-1 beta. IL-1 beta increased the IL-1 beta system and T NF-alpha mRNAs in the cerebellum and parieto-frontal cortex. IL-1 beta -induced profiles of IL-1 beta, IL-1 receptor type I and II (IL-1RI an d IL-1RII), and IL-1 receptor antagonist (IL-1Ra) mRNAs were highly in tercorrelated in the same samples. The data suggest the operation of a n IL-1 beta feedback system (IL-1 beta/IL-1RI/IL-1RI/IL-1Ra) within a brain region. The fine regulation of the CNS IL-1 beta system may depe nd on a balance between the ligand (IL-1 beta) action on the IL-1RI an d the induction of inhibitory mechanisms (IL-1RII and IL-1Ra). This ma y have implications regarding neurological diseases associated with hi gh levels of IL-1 beta in the brain. (C) 1996 Academic Press, Inc.