MODULATION OF HUMAN MICROGLIAL CELL SUPEROXIDE PRODUCTION BY CYTOKINES

Reactive oxygen intermediates (e.g., superoxide [O-2]) generated by mi croglia may play a role in host defense and injury within the central nervous system, We investigated the effect of cytokines on human micro glial cell O-2(-) production on stimulation with phorbol myristate ace tate, Priming of microglial cell cultures with interferon-gamma or tum or necrosis factor-alpha resulted in a dose- and time-dependent enhanc ement of O-2(-) production, The priming effects of these cytokines wer e mediated through a protein kinase C signal transduction pathway. In contrast, astrocytes did not generate detectable O-2(-) On phorbol myr istate acetate stimulation, Treatment of microglia with transforming g rowth factor-beta, interleukin-4, or interleukin-10 suppressed in a do se-dependent manner the priming effects of tumor necrosis factor-alpha and interferon-gamma. The results of this study have implications for understanding the mechanisms by which cytokines and microglia contrib ute to processes of host defense and neurodegeneration via generation of reactive oxygen intermediates.