Natural killer (NK) cell deficit in coronary artery disease: no aberrations in phenotype but sustained reduction of NK cells is associated with low-grade inflammation

Clin Exp Immunol. 2014 Jan;175(1):104-12. doi: 10.1111/cei.12210.

Abstract

Although reduced natural killer (NK) cell levels have been reported consistently in patients with coronary artery disease (CAD), the clinical significance and persistence of this immune perturbation is not clarified. In this study we characterized the NK cell deficit further by determining (i) differentiation surface markers and cytokine profile of NK cell subsets and (ii) ability to reconstitute NK cell levels over time. Flow cytometry was used to analyse NK cell subsets and the intracellular cytokine profile in 31 patients with non-ST elevation myocardial infarction (non-STEMI), 34 patients with stable angina (SA) and 37 healthy controls. In blood collected prior to coronary angiography, the proportions of NK cells were reduced significantly in non-STEMI and SA patients compared with controls, whereas NK cell subset analyses or cytokine profile measurements did not reveal any differences across groups. During a 12-month follow-up, the proportions of NK cells increased, although not in all patients. Failure to reconstitute NK cell levels was associated with several components of metabolic syndrome. Moreover, interleukin (IL)-6 levels remained high in patients with sustained NK cell deficit, whereas a decline in IL-6 (P < 0·001) was seen in patients with a pronounced increase in NK cells. In conclusion, we found no evidence that reduction of NK cells in CAD patients was associated with aberrations in NK cell phenotype at any clinical stage of the disease. Conversely, failure to reconstitute NK cell levels was associated with a persistent low-grade inflammation, suggesting a protective role of NK cells in CAD.

Keywords: coronary artery disease; cytokines; inflammation; leukocytes; natural killer cell.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / immunology
  • Coronary Artery Disease / pathology
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • Inflammation / blood
  • Inflammation / immunology
  • Inflammation / pathology
  • Interleukin-6 / blood*
  • Interleukin-6 / immunology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Killer Cells, Natural / pathology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / immunology
  • Myocardial Infarction / pathology

Substances

  • IL6 protein, human
  • Interleukin-6