Elevated tumor necrosis factor-α and interleukin-6 in myocardium and serum of malfunctioning donor hearts

Background - Myocardial dysfunction is a common and important problem in donor hearts. The mechanisms responsible remain unclear. We have studied the cytokines tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) in the myocardium and serum from donors with myocardial dysfunction (unused donors) and compared them with donors with good ventricular function (used donors) and patients with advanced heart failure (HF). Methods and Results - Clinical details and ventricular function were assessed in 46 donors (31 used, 15 unused). Real-time reverse transcription-polymerase chain reaction, Western blotting, and immunocytochemistry were performed on myocardium and immunoassays on serum. TNF-α mRNA was 1.6-fold higher in unused than in used donors (P<0.005) and 1.74-fold higher than in 36 patients with HF. IL-6 mRNA was 2.4-fold higher in unused than in used donors (P<0.0001) and 4.67-fold higher than in HF (P<0.0001). Western blotting showed higher TNF-α in unused (218.3±6.4, n=4 versus 187.3±5.4, n=3 OD units) than used donors (P<0.05). TNF-α expression was localized to cardiac myocytes. Serum TNF-α was higher in unused (8.72±1.3 pg/mL, n = 13) than in used (6.12 ± 0.8 pg/mL, n=25, P<0.05) donors and HF (4.0±0.4 pg/mL, n=17, P<0.005). Serum TNF-α receptors did not differ between unused (4.3±0.8 and 8.6±1.6 ng/mL, n = 10) and used (3.5±0.4 and 6.5±1.1 ng/mL, n=24) donors. There was a trend for higher serum IL-6 in unused (16.5±2.9 pg/mL, n=9) compared with used (13.9±1.6 pg/mL, n=26, P=NS) donors. Conclusions - This study documented an increase in the expression of TNF-α and IL-6 in the myocardium of all donor hearts that was more marked in the dysfunctional (unused) donor hearts. This was accompanied by similar changes in the serum. This might have important therapeutic implications.