SOLUBLE INTERLEUKIN-2-RECEPTOR LEVELS AS A MARKER OF CORONARY MICROVASCULAR DYSFUNCTION AFTER HEART-TRANSPLANTATION

Background: Immunologic mechanisms operating in a milieu of nonimmunol ogic risk factors constitute the principal stimuli that result in prog ressive cardiac allograft vasculopathy. Interleukin-2 has a central ro le in the development of cell-mediated immunity and is a key factor in the induction of a complex network of cytokines. On exposure to cytok ines, endothelial cells can undergo profound alterations of vasomotor function. In this study we characterized the relationship between coro nary microvascular function and soluble interleukin-2 receptor (sIL-2R ) levels after human heart transplantation. Methods: We studied 15 hea rt transplant recipients after an average follow-up time of 39 +/- 22 months. We measured coronary artery blood flow in an endothelium-depen dent manner with acetylcholine (50 mu g) and in an endothelium-indepen dent manner with dipyridamole (0.56 mg/kg) by intracoronary Doppler ca theter. Blood samples from the superior vena cava were drawn 3 to 12 m onths 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 en zyme-linked immunoabsorbent assay. Results: We found a significant inv erse correlation between impaired endothelium-mediated (p = 0.03) but not endothelium-independent relaxation of the coronary microvasculatur e and elevated sIL-2R levels. In heart transplant recipients without a cute rejection or an infection episode, an sIL-2R-level of more than 8 00 U/ml was defined as a cutpoint, indicating disturbed endothelium-de pendent microvascular function. Additionally, there was a conspicuous trend toward an inverse correlation between early elevated sIL-2R-leve ls and endothelium-dependent microvascular dysfunction (p = 0.06). Con clusions: The results of this study demonstrate the utility of sIL-2R, an index of immunologic activity, to be used as a marker and predicto r of impaired endothelial microvascular function in heart transplant r ecipients. These observations support the hypothesis that after heart transplantation endothelial dysfunction in the microcirculation is an immunologic phenomenon.