Synergism between interleukins 1β and 6 on noradrenergic nerves in rat myenteric plexus

BACKGROUND/AIMS: 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.