Interleukin-1 beta and tumor necrosis factor-alpha inhibit the release of [3H]-noradrenaline from isolated human atrial appendages.

In the present study, we have investigated the ability of human recombinant interleukin-1 beta (hIL-1 beta) and human recombinant tumor necrosis factor-alpha (hTNF-alpha) to modulate the stimulation-induced (S-I) outflow of [3H]-noradrenaline ([3H]-NA) from isolated superfused human atria. Pieces of human right atrial appendages were excised during routine cardiac surgery. Tissues were incubated with [3H]-NA (0.2 mumol/l) for 30 min at 37 degrees C, then inserted in a Brandel suprafusion system where the radioactivity was washed for 75 min with a Krebs-Henseleit solution at a rate of 0.4 ml/min. Thereafter, the effluent was collected for the remainder of the protocol during which two trains of electrical stimulation (50 mA intensity, 5 Hz frequency, 60 s duration, 2 ms pulses) were delivered at 10 min and 45 min (short protocol) or 85 min (long protocol). The effect of drugs on the S-I outflow of [3H]-NA was determined by adding drugs 20 min (short protocol) or 60 min (long protocol) before the second stimulation. Experiments were carried out in the continuous presence of desipramine (1 mumol/l) to prevent neuronal NA reuptake. The results showed that in human atrium, hIL-1 beta (3 ng/ml) and hTNF-alpha (0.5 ng/ml) significantly inhibited the S-I release of [3H]-NA. The inhibitory effect of hIL-1 beta was blocked by human recombinant IL-1 receptor antagonist (50 ng/ml), and by the cyclooxygenase inhibitor, diclofenac (1 mumol/l), suggesting that hIL-1 beta inhibited NA release through the formation of prostaglandins. The ability of hIL-1 beta and hTNF-alpha to inhibit NA release suggest that mediators of the immune system produced locally may modulate the activity of the sympathetic nervous system in human atrial appendages.