CONTROL OF ASTROCYTOSIS BY INTERLEUKIN-1 AND TRANSFORMING GROWTH-FACTOR-BETA-1 IN HUMAN BRAIN

Astrocytosis is a common neurocellular manifestation of brain patholog y in individuals with a variety of diseases. It is comprised of astroc ytic hyperplasia (an increase in number of astrocytes) and astrocytic hypertrophy (an increase in size of astrocytes). The precise cause (s) of astrocytosis remains unknown. We morphometrically measured the rel ative extent of astrocytosis in brains of 22 individuals who died with seven different diseases. The relative amounts of interleukin-1 (IL-1 ) and transforming growth factor-beta 1 (TGF-beta 1) immunoreactive pr oducts (IRPs) were next assessed in sections serial to those in which astrocytosis was measured because these cytokines were shown in animal and in vitro experiments to be associated with astrocytosis. The data demonstrate that astrocytosis and these cytokines were co-localized i n all examined human tissues. Relative increase in density of astrocyt es was correlated with the increase in total IL-1 but not TGF-beta 1. In contrast, the increase in size of astrocytes was correlated with TG F-beta 1 associated only with astrocytes but not with total IL-1. Both IL-1 and TGF-beta 1 IRPs were present in GFAP IRP-containing and othe r cells, as assessed by double label immunocytochemistry. These observ ations suggest that IL-1 acts on astrocytes by both, paracrine and aut ocrine mechanisms whereas, TGF-beta 1 only acts by an autocrine mechan ism. Because these correlations were statistically significant and als o because a change in number and size of astrocytes constitutes the mo st frequent response of astrocytes to several diseases or injury, we c onclude that these cytokines may mediate the most common pathological change in human brain.