Interleukin-8 Production by Macrophages From Atheromatous Plaques

Abstract

Interleukin-8 (IL-8) is a chemotactic peptide produced by macrophages that may be involved in the recruitment of inflammatory cells into atherosclerotic plaques. In vitro, IL-8 production by macrophages isolated from carotid plaques (1240±510 pg·10⁵cells⁻¹·24 h⁻¹, mean±SEM, n=6) and noncarotid plaques (4312±1588 pg·10⁵cells⁻¹·24 h⁻¹, n=9) was significantly greater than IL-8 production by blood monocytes isolated from the same patients (526±278 pg·10⁵cells⁻¹·24 h⁻¹, n=6,P<.05 and 726±384 pg·10⁵cells⁻¹·24 h⁻¹, n=9,P<.01, respectively). IL-8 produced by atherosclerotic macrophages was demonstrated to be biologically active in a neutrophil chemotaxis assay. IL-8 mRNA was detectable in plaque macrophages and blood monocytes from these patients, but blood monocytes from normal donors did not exhibit detectable IL-8 mRNA. IL-8 mRNA was localized in macrophage-rich areas of atherosclerotic plaques by in situ hybridization. These studies demonstrate that macrophages from atherosclerotic plaques show an enhanced capacity to produce IL-8 compared with normal and patient blood monocytes and that macrophages are a major site of IL-8 mRNA production in atherosclerotic plaques. These results provide further evidence for a proinflammatory role for macrophages in atherosclerosis.