IN the present study, we tested the hypothesis that interleukin (IL)-10 down-regulates human microglial cell IL-8 release by inhibiting activation of nuclear factor kappa B (NF-κB). Immunohistochemical staining demonstrated that IL-10 markedly suppressed lipopolysaccharide (LPS)-and IL-1β-stimulated IL-8 expression. NF-κB involvement was suggested by the finding that pyrrolidinedithiocarbamate, a known inhibitor of NF-κB activation, blocked LPS-and IL-1β-induced IL-8 production. Consistent with our hypothesis, IL-10 treatment of LPS-and IL-1β-stimulated microglia was associated with a marked decrease in NF-κB translocation from the cytoplasm to the nucleus.