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

Interleukins (TL)-1 alpha, beta and IL-6 may play essential roles in early inflammatory processes in response to degenerating cholinergic cells observ ed in the basal forebrain of Alzheimer patients. To address this question i n vivo, two distinct lesion paradigms were used. A specific and selective b asal forebrain cholinergic cell loss was achieved by a single intracerebrov entricular application of the cholinergic immunotoxin, 192IgG-saporin. Intr ahippocampal 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 alph a, beta/IL-6 mRNA, Western analysis, RT-PCR, and double labeling immunocyto chemistry were applied. In the intact brain, IL-6, IL-1 alpha and IL-1 beta demonstrated a constitutive expression in neurons. Following cholinergic l esion 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 i n astroglial cells only. In contrast, hippocampal administration of lipopol ysaccharides/interferon-gamma resulted in expression of IL-1 alpha in micro glial but not astroglial cells. These in vivo studies clearly demonstrate t hat 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 s eems 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 co ndition in the brain. (C) 1999 Wiley-Liss, Inc.