Increased interleukin-6 expression by microglia from brain of aged mice

Over expression of inflammatory cytokines in the brain may establish a stat e that is permissive to the onset of neurodegenerative disease. Because the occurrence of certain neurodegenerative diseases increases with age, in th e present study we examined the expression of the inflammatory cytokine, in terleukin-6 (IL-6), in the brain of aged mice. In an initial experiment, IL -6 was measured in crude protein extracts from brains of juvenile (I-month- old), adult (3-month-old), and aged (24-month-old) male BALB/c mice. The co ncentration of IL-6 in crude protein extracts from the cerebellum, cerebral cortex, and hippocampus increased with age. The increase in IL-6 was discr ete, as levels in the hypothalamus were not age-dependent. To begin evaluat ing spontaneous IL-6 production in aging, glial cells were cultured from br ains of neonate, adult, and aged mice. An age-associated increase in IL-6 m RNA and supernatant IL-6 concentration was evident, indicating glia from ag ed mice spontaneously express high levels of IL-6 relative to glia from adu lt and neonate mice. Flow cytometric analysis revealed that cultures establ ished from aged brain compared to either adult or neonate brain comprised m ore microglia (i.e., MAC-1-positive cells). Furthermore, the proportion of microglia that was positive for IL-6 increased with age, whereas the propor tion of astrocytes that were positive for IL-6 was not age-dependent. The p resent results suggest that IL-6 increases in the mouse brain with age, and that microglia cultured from aged mice spontaneously produce more IL-6 tha n those from neonate or adult mice. Therefore, microglia may contribute to the increased level of IL-6 present in aged brain. (C) 1999 Elsevier Scienc e B.V. All rights reserved.