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The Journal of Immunology, 1998, 160: 1944-1948.
Copyright © 1998 by The American Association of Immunologists

Cytokine Regulation of Human Microglial Cell IL-8 Production1

Laura C. Ehrlich*, Shuxian Hu*,{ddagger}, Wen S. Sheng*, Richard L. Sutton{dagger},{ddagger}, Gaylan L. Rockswold{dagger},{ddagger}, Phillip K. Peterson*,{ddagger} and Chun C. Chao2,*,{ddagger}

* Neuroimmunobiology and Host Defense Laboratory, and {dagger} Neurotrauma Research Laboratory, Minneapolis Medical Research Foundation, and {ddagger} University of Minnesota Medical School, Minneapolis, MN 55404

IL-8 involvement in neutrophil activation and chemotaxis may be important in inflammatory responses within the central nervous system, secondary to meningitis, encephalitis, and traumatic injury. The source of IL-8 within the brain during these inflammatory processes, however, is unknown. To explore the role of microglia in the production of IL-8, human fetal microglia, which are the resident macrophages of the brain, were treated with LPS and pro- and anti-inflammatory cytokines to determine their effects on IL-8 production. We found that IL-8 protein levels increased in response to LPS or IL-1ß, or to TNF-{alpha}, which also corresponded to elevated IL-8 mRNA levels by RT-PCR. Pretreatment with IL-4, IL-10, or TGF-ß1 potently inhibited the stimulatory effects of these proinflammatory agents. These findings indicate that human microglia synthesize IL-8 in response to proinflammatory stimuli, and that anti-inflammatory cytokines down-regulate the production of this chemokine. These results may have important therapeutic implications for certain central nervous system insults involving inflammation.




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