Effects of microglia-derived cytokines on astrocyte proliferation

Recent studies have suggested that cytokines, such as interleukin-l(IL-l), tumor necrosis factor(TNF)α, or interferon(IFN) γ, play a role in the development of astrocytic gliosis. In this study, we examined the effects of these cytokines on the proliferation of purified astrocytes in vitro, using the colorimetric assay, bromodeoxyuridine uptake by astrocytes, and changes in the amount of the S-100 β protein as markers of astrocyte proliferation. The effects of a crude supernatant from microglia enriched cultures (Mi-Sup) also were examined. In contrast to previous reports, these recombinant cytokines did not induce proliferation of purified mouse astrocytes. However, stimulation of astrocytes with Mi-Sup increased all the markers for astrocyte proliferation, which could not be blocked by the addition of anti-IL-1, IL-6, IFNγ or TGFβ antibodies. Thus, it appears that microglia produce factors, other than the above cytokines, which induce the proliferation of astrocytes in vitro. These factors may have a role in the development of gliosis in various pathologic conditions of the central nervous system.