INVOLVEMENT OF EICOSANOIDS AND MACROPHAGE-LIKE CELLS IN CYTOKINE-MEDIATED CHANGES IN RAT MYENTERIC NERVES

Background & Aims: Proinflammatory cytokines alter function in enteric nerves, but little is known about underlying mechanisms. This study w as designed to investigate the roles of prostanoids and of macrophage- like cells in cytokine-induced suppression of [H-3]norepinephrine rele ase from rat myenteric plexus. Methods: The release of H-3 from jejuna l longitudinal muscle-myenteric plexus preparations that had been load ed with [H-3]norepinephrine was measured. Measurements of H-3 release as well as concentrations of prostaglandin E(2) and leukotriene were m ade in preparations exposed to interleukin 1 beta plus interleukin 6 a nd in the presence or absence of piroxicam, B-lipoxygenase inhibitor M K886, cycloheximide, or cyclosporin A. An ultrastructural analysis was also performed to investigate the presence of macrophage-like cells i n the myenteric plexus. Results: Interleukin 1 beta plus interleukin 6 suppressed H-3 release and caused an increase in tissue prostaglandin E(2) but not leukotriene E(4). Piroxicam and cycloheximide but not MK 886 attenuated the cytokine-induced increase in prostaglandin E(2) and the suppression of [H-3]norepinephrine release. Ultrastructural analy sis showed macrophage-like cells in the plexus, and the cytokine effec ts were inhibited by cyclosporin A. Conclusions: Prostanoids but not l eukotrienes mediate the cytokine-induced suppression of norepinephrine release, and the results of this study suggest that macrophage-like c ells are also involved.