INTERLEUKIN-8 PRODUCTION BY MACROPHAGES FROM ATHEROMATOUS PLAQUES

Interleukin-8 (IL-8) is a chemotactic peptide produced by macrophages that may be involved in the recruitment of inflammatory cells into ath erosclerotic plaques. In vitro, IL-8 production by macrophages isolate d from carotid plaques (1240+/-510 pg . 10(5) cells(-1). 24 h(-1), mea n+/-SEM, n=6) and noncarotid plaques (4312+/-1588 pg . 10(5) cells(-1) . 24 h(-1), n=9) was significantly greater than IL-8 production by blo od monocytes isolated from the same patients (526+/-278 pg . 10(5) cel ls(-1). 24 h(-1), n=6, P<.05 and 726+/-384 pg . 10(5) cells(-1). 24 h( -1), n=9, P<.01, respectively). IL-8 produced by atherosclerotic macro phages was demonstrated to be biologically active in a neutrophil chem otaxis 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 macr ophage-rich areas of atherosclerotic plaques by in situ hybridization. These studies demonstrate that macrophages from atherosclerotic plaqu es 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 furt her evidence for a proinflammatory role for macrophages in atheroscler osis.