IL-1 beta and IL-6 excite neurones and suppress cholinergic neurotransmission in the myenteric plexus of the guinea pig

The effects of the inflammatory mediators interleukin-1 beta (IL-1 beta) an d interleukin-6 (IL-6) on myenteric neurones were investigated by intracell ular recordings in a conventional myenteric plexus preparation of guinea pi g ileum. Micropressure ejection of IL-1 beta and IL-6 (10(-7) mol L-1) both caused an excitatory effect in, respectively, 19% (13/70) and 7% (5/70) of the myenteric neurones. The IL-1 beta -induced depolarizations were inhibi ted by superfusion of the IL-1 beta receptor antagonist. The responses seen were tetrodotoxin-resistant, indicating a direct neuronal effect. Response s to both cytokines were seen in nitric oxide synthase-immunoreactive as we ll as choline acetyltransferase-immunoreactive neurones. In addition, both IL-1 beta and IL-6 reversibly caused a presynaptic inhibition of acetylchol ine release from cholinergic nerve terminals. Both cytokines had no effect on the slow excitatory postsynaptic potentials. Therefore, we can conclude that the inflammatory mediators IL-1 beta and IL-6 can act as excitatory ne uromodulators of gastrointestinal motility through direct excitatory action s on a subset of myenteric neurones and through the presynaptic inhibition of acetylcholine release.