The effects of interleukin (IL)- lα, IL- 1β and TNFα on prostaglandin-E2 synthesis in Madin-Darby canine kidney (MDCK) cells were investigated. IL-lβ time- and dose-dependently stimulated prostaglandin-E2 synthesis. While TNFα produced a comparatively small but significant stimulation of PGE2 release, coincubation of IL-lβ with TNFα produced a marked synergistic stimulation of PGE2 release. The effect of IL-lβ and of IL-1β and TNFα was apparent as early as after 2 h of incubation. The enhanced PGE2 synthesis was inhibited by indomethacin as well as actinomycin D, while cycloheximide surprisingly potentiated PGE2 synthesis in response to both IL-1β and TNFα. IL-1α alone was ineffective in stimulating a significant release of PGE2 at concentrations as high as 10 nM. However, it also showed a marked synergistic interaction with TNFα in stimulating PGE2 release.
