Differential injury-dependent glial expression of interleukins-1?, ?, and interleukin-6 in rat brain

Abstract

Interleukins (IL)-1 alpha, beta and IL-6 may play essential roles in early inflammatory processes in response to degenerating cholinergic cells observed in the basal forebrain of Alzheimer patients. To address this question in vivo, two distinct lesion paradigms were used. A specific and selective basal forebrain cholinergic cell loss was achieved by a single intracerebroventricular application of the cholinergic immunotoxin, 192IgG-saporin. Intrahippocampal injection of lipopolysaccharide and interferon-gamma was used to produce an exogenously-induced acute inflammation in the brain. In order to disclose the lesion-induced temporal cascade of the expression pattern of IL-1 alpha, IL-1 beta, and IL-6, and the cell types expressing IL-1 alpha, beta/IL-6 mRNA, Western analysis, RT-PCR, and double labeling immunocytochemistry were applied. In the intact brain, IL-6, IL-1 alpha and IL-1 beta demonstrated a constitutive expression in neurons. Following cholinergic lesion neither IL-1 beta nor IL-6 expression could be detected in any of the activated glial cell types, whereas IL-1 alpha was found to be expressed in astroglial cells only. In contrast, hippocampal administration of lipopolysaccharides/interferon-gamma resulted in expression of IL-1 alpha in microglial but not astroglial cells. These in vivo studies clearly demonstrate that the cellular expression of IL-1 alpha, IL-1 beta, and IL-6 in the brain is differentially regulated depending on the kind of injury producing the inflammatory response in the brain. The data suggest that each glial cell seems to be equally capable of expressing a number of various cytokines, but it depends on the kind of stimulus which temporal and cellular cascade of cytokine expression pattern is initiated under a particular pathological condition in the brain.