Peripheral Blood Cytokine Levels After Acute Myocardial Infarction: IL-1β- and IL-6-Related Impairment of Bone Marrow Function

Circ Res. 2017 Jun 9;120(12):1947-1957. doi: 10.1161/CIRCRESAHA.116.309947. Epub 2017 May 10.


Rationale: Intracoronary infusion of bone marrow (BM) mononuclear cells after acute myocardial infarction (AMI) has led to limited improvement in left ventricular function. Although experimental AMI models have implicated cytokine-related impairment of progenitor cell function, this response has not been investigated in humans.

Objective: To test the hypothesis that peripheral blood (PB) cytokines predict BM endothelial progenitor cell colony outgrowth and cardiac function after AMI.

Methods and results: BM and PB samples were collected from 87 participants 14 to 21 days after AMI and BM from healthy donors was used as a reference. Correlations between cytokine concentrations and cell phenotypes, cell functions, and post-AMI cardiac function were determined. PB interleukin-6 (IL-6) negatively correlated with endothelial colony-forming cell colony maximum in the BM of patients with AMI (estimate±SE, -0.13±0.05; P=0.007). BM from healthy individuals showed a dose-dependent decrease in endothelial colony-forming cell colony outgrowth in the presence of exogenous IL-1β or IL-6 (P<0.05). Blocking the IL-1R or IL-6R reversed cytokine impairment. In AMI study participants, the angiogenic cytokine platelet-derived growth factor BB glycoprotein correlated positively with BM-derived colony-forming unit-endothelial colony maximum (estimate±SE, 0.01±0.002; P<0.001), multipotent mesenchymal stromal cell colony maximum (estimate±SE, 0.01±0.002; P=0.002) in BM, and mesenchymal stromal cell colony maximum in PB (estimate±SE, 0.02±0.005; P<0.001).

Conclusions: Two weeks after AMI, increased PB platelet-derived growth factor BB glycoprotein was associated with increased BM function, whereas increased IL-6 was associated with BM impairment. Validation studies confirmed inflammatory cytokine impairment of BM that could be reversed by blocking IL-1R or IL-6R. Together, these studies suggest that blocking IL-1 or IL-6 receptors may improve the regenerative capacity of BM cells after AMI.

Clinical trial registrations: URL: Unique identifier: NCT00684060.

Keywords: bone marrow cells; cell therapy; interleukin-1; interleukin-6; myocardial infarction.

Publication types

  • Clinical Trial

MeSH terms

  • Bone Marrow / physiology
  • Bone Marrow Cells / physiology*
  • Cells, Cultured
  • Cytokines / blood*
  • Female
  • Humans
  • Interleukin-1beta / blood*
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Myocardial Infarction / blood*
  • Myocardial Infarction / diagnosis


  • Cytokines
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6

Associated data