Synergism between interleukins 1 beta and 6 on noradrenergic nerves in rat myenteric plexus.
OBJECTIVE
Because levels of interleukins 1 beta and 6 (IL-1 beta and IL-6) are elevated during intestinal Trichinella spiralis infection, they may mediate the changes in enteric neural function in that model. IL-1 beta suppresses norepinephrine release from the myenteric plexus, but the effect of IL-6 is unknown. Therefore, we investigated the effects of IL-6 alone and in combination with IL-1 beta on norepinephrine release.


METHODS
Longitudinal muscle myenteric plexus or myenteric nerve varicosity preparations from jejunum of noninfected rats were loaded with [3H]norepinephrine, and 3H release was measured after a preincubation with or without human recombinant IL-6, alone or in combination with human recombinant IL-1 beta.


RESULTS
1 ng/mL of IL-6 augmented 3H release, 100 ng/mL suppressed 3H release, whereas 10 ng/mL had no effect. However, IL-6 (10 ng/mL) plus a subthreshold concentration of human recombinant IL-1 beta significantly suppressed 3H release, and this was abolished by adding anti-IL-6 antibody or an IL-1 receptor antagonist.


CONCLUSIONS
Because 3H release reflects [3H]norepinephrine release, our results show that IL-6 exerts a dual effect on norepinephrine release. Furthermore, there is synergism between IL-1 beta and IL-6 resulting in suppression of norepinephrine release. Therefore, both cytokines may contribute to the suppression of norepinephrine release observed in the inflamed intestine.
Rühl
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A
Intestinal Diseases Research Program, McMaster University Medical Centre, Hamilton, Ontario, Canada.
Hurst
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S
Collins
S M
SM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects* / Q000378:metabolism*; D009420:Nervous System / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins
D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D009638:Norepinephrine