Regulation of brain interleukin-1 beta (IL-1 beta) system mRNAs in response to pathophysiological concentrations of IL-1 beta in the cerebrospinal fluid.

Abstract

Interleukin-1 beta (IL-1 beta) is released during pathophysiological processes. IL-1 beta induces neurological manifestations when administered into the cerebrospinal fluid (CSF) at pathophysiological concentrations detected during central nervous system (CNS) infections and other neurological disorders. In the present study, we investigated the regulation of the IL-1 beta system in the CNS in response to the chronic intracerebroventricular (icv) microinfusion of IL-1 beta at estimated pathophysiological concentrations in the CSF. IL-1 receptor type I (IL-1RI), IL-1 receptor antagonist (IL-1Ra), and IL-1 beta mRNAs were determined by sensitive RNase protection assays in brain target regions for IL-1 beta (cerebellum, parieto-frontal cortex, hippocampus, and midbrain). The results show that chronic icy microinfusion of IL-1 beta induced significant anorexia, increased the cerebellar IL-1RI mRNA content, increased IL-1Ra and IL-1 beta mRNAs levels in the cerebellum > midbrain > cortex > hippocampus, and induced profiles of IL-1RI mRNA, IL-1Ra mRNA, and IL-1 beta mRNA that were highly intercorrelated. On the other hand, levels of rat glyceraldehyde 3-phosphate dehydrogenase mRNA and 18S rRNA were fairly constant, and heat-inactivated IL-1 beta had no effect on food intake or on IL-1RI, IL-1Ra, and IL-1 beta mRNAs levels in any brain region. The data suggest the operation of an IL-1 beta feedback system (IL-1 beta/ IL-1Ra/IL-1RI) in brain regions. Dysregulation of the CNS IL-1 beta feedback system may have pathophysiological significance. This may be reflected, for example, in the pathogenicity and severity of neurological diseases, such as CNS infections.