Interleukin-1 Beta and Tumor Necrosis Factor-alpha Inhibit the Release of [3H]-noradrenaline from Mice Isolated Atria

In the present study, we have investigated the ability of four cytokines, interleukin-1 beta, interleukin-2, interleukin-6 and tumor necrosis factor-alpha, to modulate the stimulation-induced outflow of radioactivity from isolated superfused mouse atria which where pre-incubated with [3H]-noradrenaline. The tissues were subjected twice to field stimulation (5 Hz frequency, 50 mA intensity, 2 ms pulses for 60 s) and the drugs were added prior to the second stimulation in order to assess their modulatory effects. The results show that mouse recombinant interleukin-1 beta and tumor necrosis factor-alpha inhibited the stimulation-induced release of radioactivity from the isolated mouse atria. The effect of interleukin-1 beta was blocked by a human recombinant interleukin-1 receptor antagonist. The inhibitory effect of interleukin-1 beta was also abolished by the cyclooxygenase inhibitor, diclofenac (1 mumol/l) suggesting that the action of interleukin-1 beta might be mediated through the formation of prostaglandins. The effect of interleukin-1 beta appears to be time-dependent, since a stronger inhibition of radio-activity release was observed when the incubation time was increased from 20 to 65 minutes before the second stimulation. Interleukin-2 and interleukin-6 were ineffective in modulating release under these experimental conditions. The ability of interleukin-1 beta and tumor necrosis factor-alpha to inhibit noradrenaline release suggests that mediators of the immune system produced locally may modulate the activity of the sympathetic nervous system.