DIETARY MARINE LIPIDS SUPPRESS CONTINUOUS EXPRESSION OF INTERLEUKIN-1-BETA GENE-TRANSCRIPTION

n-3 Polyunsaturated fatty acids abundant in marine lipids suppress cer tain inflammatory and immune reactions, and dietary marine lipid suppl ements have antiinflammatory effects in experimental and human autoimm une disease. Previous work by other investigators demonstrated that di etary marine lipid supplements suppressed production of cytokines from stimulated human peripheral blood mononuclear cells ex vivo. The pres ent study further documents the ability of n-3 fatty acids to inhibit cytokine formation, and in part defines the mechanism of the inhibitio n of production of interleukin-1 beta (IL-1 beta) by dietary n-3 fatty acid. Female BALB/c mice were each fed a fat-free balanced diet to wh ich was added either a refined fish oil (FO) preparation as a source o f n-3 fatty acid, or beef tallow (BT), which consisted primarily of sa turated and monoenoic fatty acids. After ingesting the experimental di ets for periods ranging from 3 to 12 wk, spleen cell preparations were stimulated ex vivo with either lipopolysaccharide (LPS) or phorbol 12 -myristate 13-acetate (PMA), and proIL-1 beta mRNA (IL-1 beta mRNA) wa s measured by northern analysis. Levels of IL-1 beta mRNA in both LPS- and PMA-stimulated cells from PT-fed mice were elevated to a greater extent than in cells from FO-fed mice, at most concentrations of LPS a nd PMA. Stability of LPS-stimulated mRNA levels after actinomycin D wa s similar for PT and FO groups, indicating that lower levels of IL-l m RNA with FO groups was related to suppressed IL-l gene transcription a nd not due to accelerated transcript degradation. Nuclear run-on trans cription assays revealed a more transient expression of the IL-1 beta gene in LPS-stimulated spleen cells from FO-fed mice compared to cells from PT-fed mice. We conclude that dietary marine lipids reduce trans ient expression of the IL-1 beta gene in stimulated splenic monocytic cells. Preliminary results from nuclear run-on transcription assays in dicate that n-3 fatty acids may not change the initial rate of gene tr anscription but may promote more rapid shutting down of transcription of this gene after induction than do alternative lipids.