In vivo regulation of the IL-1 beta system (ligand, receptors I and II, receptor accessory protein, and receptor antagonist) and TNF-alpha mRNAs in specific brain regions

Interleukin-1 beta (IL-1 beta) acts directly in the central nervous system (CNS). Here, using a novel behavioral-molecular approach, we report the regulation of the complete IL-1 beta system (ligand, receptors, receptor accessory protein, and receptor antagonist) and TNF-alpha mRNAs in the CNS in response to the chronic intracerebroventricular microinfusion of IL-1 beta. IL-1 beta increased the IL-1 beta system and TNF-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 and IL-1RII), and IL-1 receptor antagonist (IL-1Ra) mRNAs were highly intercorrelated in the same samples. The data suggest the operation of an 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 depend on a balance between the ligand (IL-1 beta) action on the IL-1RI and the induction of inhibitory mechanisms (IL-1RII and IL-1Ra). This may have implications regarding neurological diseases associated with high levels of IL-1 beta in the brain. (C) 1996 Academic Press, Inc.