EFFECTS OF MICROGLIA-DERIVED CYTOKINES ON ASTROCYTE PROLIFERATION

Recent studies have suggested that cytokines, such as interleukin-1(IL -1), tumor necrosis factor(TNF)alpha, or interferon(IFN) gamma, play a role in the development of astrocytic gliosis. In this study, we exam ined the effects of these cytokines on the proliferation of purified a strocytes in vitro, using the colorimetric assay, bromodeoxyuridine up take by astrocytes, and changes in the amount of the S-100 beta protei n as markers of astrocyte proliferation. The effects of a crude supern atant from microglia enriched cultures (Mi-Sup) also were examined. In contrast to previous reports, these recombinant cytokines did not ind uce proliferation of purified mouse astrocytes. However, stimulation o f astrocytes with Mi-Sup increased all the markers for astrocyte proli feration, which could not be blocked by the addition of anti-IL-1, IL- 6, IFNgamma or TGFbeta antibodies. Thus, it appears that microglia pro duce factors, other than the above cytokines, which induce the prolife ration of astrocytes in vitro. These factors may have a role in the de velopment of gliosis in various pathologic conditions of the central n ervous system.