Involvement of eicosanoids and macrophage-like cells in cytokine-mediated changes in rat myenteric nerves

Abstract

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 E 2 and leukotriene were made in preparations exposed to interleukin 1β 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 1β plus interleukin 6 suppressed 3H release and caused an increase in tissue prostaglandin E 2 butnot leukotriene E 4. Piroxicam and cycloheximide but not MK886 attenuated the cytokine-induced increase in prostaglandin E 2 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.