Peripheral blood mononuclear cell production of interleukin-8 and IL-8-dependent neutrophil function in hypercholesterolemic patients

Interleukin-8 is a cytokine produced by mononuclear cells that is involved in polymorphonuclear neutrophil leukocyte (PMN) recruitment and activation. Several studies have previously demonstrated a leukocyte activation during hypercholesterolemia and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) r eductase inhibitors have been found to play a role in the prevention of ath erothrombotic disease. The purpose of this study was to determine interleuk in-8 (IL-8) mRNA expression and ex vivo production from peripheral blood mo nonuclear cells (PBMCs) and IL-8-dependent PMN activation of hypercholester olemic (HC) patients with respect to normocholesterolemic (NC) subjects. Us ing Northern blot analysis, we found a four- and threefold increase in the amount of IL-8 transcript in PBMC from HC patients, in unstimulated and LPS stimulated cultures, respectively. A specific immunoassay showed a corresp ondingly significant increase of IL-8 immunoactivity in the conditioned med ium of PBMC from HC subjects as compared with controls (unstimulated PBMC: 15 +/- 4 vs. 4.2 +/- 3 ng/ml; P < 0.0001; LPS stimulated PBMC: 65.3 +/- 8 v s. 36.6 +/- 9 ng/ml; P < 0.0001). PMN of HC patients stimulated with IL-8 s howed a reduced elastase release with respect to NC subjects before physiol ogical granule release after f-Met-Leu-Phe (fMLP) treatment. These results indicate an upregulation of the IL-8 system in dyslipidemic patients and pr ovide evidence for ongoing in vivo IL-8-dependent PMN activation during hyp ercholesterolemia. (C) 1999 Elsevier Science Ireland Ltd. All rights reserv ed.