Interleukin-1 Receptors in the Brain: Characterization by Quantitative in Situ Autoradiography

Abstract

Autoradiography was performed on mouse brain cryosections to localize interleukin-1 (IL-1) receptors in the mouse brain and pituitary gland and to identify the cell types expressing these receptors. lnterleukin-1 receptor binding sites were mapped in the mouse central nervous system (CNS) with [¹²⁵I]IL-1α and [¹²⁵I]IL-1β. IL-1 receptors were detected in high density in the dentate gyrus of the hippocampus, choroid plexus, meninges, and anterior pituitary. IL-1 receptors are also expressed in the frontoparietal cortex at very low density. Both neurons and glial cells were shown to express IL-1 receptors. An intrahippocampal injection of colchicine, a selective neurotoxin, induced the concurrent disappearance of neuronal cells and [¹²⁵I]IL-1α binding in the hippocampus. This treatment established that IL-1 bound to the neurons of the dentate gyrus. IL-1 receptors on glial cells were not detected in situ in the CNS under basal conditions. However, [¹²⁵I]IL-1α bound to glial cells at the site of astrogliosis induced by a local mechanical injury. These results suggest that activated astrocytes express IL-1 receptors. Furthermore, the results of histoautoradiography of [¹²⁵I]IL-1α binding on astrocyte and microglial cultures showed that astrocytes express IL-1 receptors in vitro. The biochemical characterization of IL-1 binding in the dentate gyrus was achieved by quantitative in situ autoradiography. in the dentate gyrus IL-1 bound to a single class of receptor with characteristics similar to those of the receptor expressed on immune cells (K_d = 0.3 ± 0.2 nM, B_max, 60 ± 10 fmol/mg protein). Competition experiments with IL-1α and IL-1β showed that the neuronal receptor characteristics were similar to those of the type I IL-1 receptor, which binds the two isoforms of IL-1 with the same affinity. Regulation of IL-1 receptor density in the CNS and pituitary was studied after peripheral injection of LPS. Stimulation of IL-1 synthesis by LPS was shown to induce a major decrease in the number of receptors available for IL-1 binding in the CNS. A decrease of 84 ± 9% was observed in the dentate gyrus and in the choroid plexus, but no change occurred in the pituitary gland.