Effects of human recombinant interleukins on stimulation-evoked noradrenaline overflow from the rat perfused spleen.
Experiments were carried out in the isolated spleen of the rat to study in a lymphoid organ the influence of interleukins (ILs) on noradrenaline release. Spleens were perfused with Tyrode's solution and the overflow of endogenous noradrenaline was determined by HPLC with electrochemical detection. Perivascular electrical stimulation (4 or 10 Hz, 20-28 mA, 2 min) caused an increase in noradrenaline overflow and in perfusion pressure, both of which were markedly reduced by perfusion with Ca(2+)-free solution, abolished by tetrodotoxin, unaffected by hexamethonium, and subject to alpha 2-adrenoceptor- and muscarinic receptor-mediated modulation as shown by the effects of rauwolscine and methacholine. Human recombinant IL-1 beta and IL-2 and mouse recombinant IL-2 10 ng/ml failed to affect the evoked overflow of noradrenaline after an exposure time of 15 min. In contrast, human recombinant IL-1 beta and IL-2 0.1 ng/ml reduced the evoked overflow after exposure for 80 min; the inhibition tended to increase 30 min later despite washout. Murine recombinant IL-2 1.2 ng/ml caused no change after contact with the tissue for 80 min but there was an inhibition 30 min later after washout. Human recombinant IL-6 (0.1 ng/ml) caused no significant change. The inhibitory effect of low concentrations of IL-1 beta and IL-2 supports the idea that locally produced mediators of the immune system may affect neuronal function.
Bognar
I T
IT
Pharmakologisches Institut der Universität, Mainz, Germany.
Albrecht
S A
SA
Farasaty
M
M
Schmitt
E
E
Seidel
G
G
Fuder
H
H
D000818:Animals; D004347:Drug Interactions; D004558:Electric Stimulation; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007552:Isotonic Solutions; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects* / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D007552:Isotonic Solutions; D011994:Recombinant Proteins; C037692:Tyrode's solution; D016210:Methacholine Chloride; D015016:Yohimbine; D009638:Norepinephrine