Soluble interleukin-2-receptor levels as a marker of coronary microvascular dysfunction after heart transplantation.
BACKGROUND
Immunologic mechanisms operating in a milieu of nonimmunologic risk factors constitute the principal stimuli that result in progressive cardiac allograft vasculopathy. Interleukin-2 has a central role in the development of cell-mediated immunity and is a key factor in the induction of a complex network of cytokines. On exposure to cytokines, endothelial cells can undergo profound alterations of vasomotor function. In this study we characterized the relationship between coronary microvascular function and soluble interleukin-2 receptor (sIL-2R) levels after human heart transplantation.


METHODS
We studied 15 heart transplant recipients after an average follow-up time of 39+/-22 months. We measured coronary artery blood flow in an endothelium-dependent manner with acetylcholine (50 microg) and in an endothelium-independent manner with dipyridamole (0.56 mg/kg) by intracoronary Doppler catheter. Blood samples from the superior vena cava were drawn 3 to 12 months after transplantation (early value) and at time of the coronary artery flow measurement (present value). Coronary artery flow reserve was correlated to sIL-2R levels, which were determined by use of an enzyme-linked immunoabsorbent assay.


RESULTS
We found a significant inverse correlation between impaired endothelium-mediated (p = 0.03) but not endothelium-independent relaxation of the coronary microvasculature and elevated sIL-2R levels. In heart transplant recipients without acute rejection or an infection episode, an sIL-2R-level of more than 800 U/ml was defined as a cutpoint, indicating disturbed endothelium-dependent microvascular function. Additionally, there was a conspicuous trend toward an inverse correlation between early elevated sIL-2R-levels and endothelium-dependent microvascular dysfunction (p = 0.06).


CONCLUSIONS
The results of this study demonstrate the utility of sIL-2R, an index of immunologic activity, to be used as a marker and predictor of impaired endothelial microvascular function in heart transplant recipients. These observations support the hypothesis that after heart transplantation endothelial dysfunction in the microcirculation is an immunologic phenomenon.
Weis
M
M
Medical Clinic I, University Medical Center Grosshadern, Munich, Germany.
Hartmann
A
A
Scheuermann
E H
EH
Olbrich
H G
HG
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003326:Coronary Circulation; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007111:Immunity, Cellular; D016014:Linear Models; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000097:blood*; D013223:Statistics as Topic; D014664:Vasodilation
D015415:Biomarkers; D015375:Receptors, Interleukin-2