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.
Foucart
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S
Départment de Physiologie, Faculté de Médecine, Université de Montréal, (Québec), Canada.
Abadie
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C
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D009638:Norepinephrine