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-kappaB). Immunohistochemical staining demonstrated that IL-10 markedly suppressed lipopolysaccharide (LPS)- and IL-1beta-stimulated IL-8 expression. NF-kappaB involvement was suggested by the finding that pyrrolidinedithiocarbamate, a known inhibitor of NF-kappaB activation, blocked LPS- and IL-1beta-induced IL-8 production. Consistent with our hypothesis, IL-10 treatment of LPS- and IL-1beta-stimulated microglia was associated with a marked decrease in NF-kappaB translocation from the cytoplasm to the nucleus.