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

Background-Myocardial dysfunction is a common and important problem in dono r hearts. The mechanisms responsible remain unclear. We have studied the cy tokines tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-G) in the m yocardium 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-polymer ase chain reaction, Western blotting, and immunocytochemistry were performe d on myocardium and immunoassays on serum. TNF-alpha mRNA was 1.6-fold high er 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 dono rs (P<0.0001) and 4.67-fold higher than in HF (P<0.0001). Western blotting showed higher TNF-<alpha> in unused (218.3+/-6.4, n=4 versus 187.3+/-5.4, n =3 OD units) than used donors (P<0.05). TNF-<alpha> expression was localize d to cardiac myocytes. Serum TNF-alpha 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-alpha receptors did not differ betwe en 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=34) donors. There was a trend for higher serum IL-6 in unus ed (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-alph a and IL-6 in the myocardium of all donor hearts that was more marked in th e dysfunctional (unused) donor hearts. This was accompanied by similar chan ges in the serum. This might have important therapeutic implications.