- BACKGROUND & AIMS: Proinflammatory cytokines alter function in enteric nerves, but little is known about underlying mechanisms. This study was designed to investigate the roles of prostanoids and of macrophage-like cells in cytokine-induced suppression of [3H]norepinephrine release from rat myenteric plexus. METHODS: The release of 3H from jejunal longitudinal muscle-myenteric plexus preparations that had been loaded with [3H]norepinephrine was measured. Measurements of 3H release as well as concentrations of prostaglandin E2 and leukotriene were made in preparations exposed to interleukin 1 beta plus interleukin 6 and in the presence or absence of piroxicam, 5-lipoxygenase inhibitor MK886, cycloheximide, or cyclosporin A. An ultrastructural analysis was also performed to investigate the presence of macrophage-like cells in the myenteric plexus. RESULTS: Interleukin 1 beta plus interleukin 6 suppressed 3H release and caused an increase in tissue prostaglandin E2 but not leukotriene E4. Piroxicam and cycloheximide but not MK886 attenuated the cytokine-induced increase in prostaglandin E2 and the suppression of [3H]norepinephrine release. Ultrastructural analysis showed macrophage-like cells in the plexus, and the cytokine effects were inhibited by cyclosporin A. CONCLUSIONS: Prostanoids but not leukotrienes mediate the cytokine-induced suppression of norepinephrine release, and the results of this study suggest that macrophage-like cells are also involved.