Copyright © 1992, American Society for Microbiology Expression of Interleukin-8 by Lipopolysaccharide-Stimulated

Interleukin-8 (IL-8) is a potent neutrophil chemoattractant, produced by a variety of immune and nonimmune cells in response to exogenous and host-derived inflammatory stimuli. We demonstrate here that a suspension ofnormal bone marrow mononuclear cells, consisting principally of myeloid precursors, produces IL-8 in response to stimulation with lipopolysaccharide (LPS). IL-8-specific mRNA is rapidly induced, being detected first 30 min after stimulation. IL-8 is detected by enzyme-linked immunosorbent assay within 2 h of stimulation, with steady a increase in its level through 72 h. Further studies demonstrated that LPS could serve as a primary stimulus for the expression of IL-8, since LPS challenge in the presence of cycloheximide resulted in superinduction of bone marrow mononuclear cell-derived IL-8 mRNA. These investigations suggest that the stimulatory effect of LPS is independent of other cytokines such as IL-10. When compared with LPS, I-1,1 proved to be a weak signal for the expression of IL-8 by bone marrow mononuclear cells. In a dose-response study, the maximum stimulatory concentration of IL-11 (300 pg/ml) resulted in the production of 500 pg of IL-8 per 106 cells, whereas 1,ug of LPS resulted in the production of 5.5 ng/106 cells. Although IL-11 was not a particularly potent stimulus for IL-8 production by bone marrow mononuclear cells, peripheral blood mononuclear cells were highly susceptible to IL-1p challenge. In addition, the potential dependence of LPS-induced marrow-derived IL-8 production on the intermediate synthesis of IL11 was further investigated