Fish oil enhances macrophage tumour necrosis factor-alpha mRNA expression at the transcriptional level

The impact of fish oil on tumour necrosis-alpha (TNF-alpha) production by macrophages stimulated by lipopolysaccharide (LPS) was examined in mice. Animals were fed high fat diets (20% fat wt/wt) rich in fish oil, corn oil or coconut oil for 4 weeks; a group of mice fed a low fat diet (5%) was included. Peritoneal macrophages were incubated with or without LPS for 24 h and the level of TNF-alpha measured in the culture medium. TNF-alpha mRNA was measured every 30 min for 2 h after addition of LPS by dot blot hybridization. Post-transcriptional studies were performed using actinomycin D and/or cycloheximide in the fish oil and corn oil groups. Production of TNF-a by macrophages was increased by more than 10-fold in the fish oil group compared to other groups; no difference was seen between low fat, corn oil and coconut oil groups. Compared to the low fat diet, higher levels of TNF-alpha mRNA were detected in the fish oil group (2.3-fold), and to a lesser extent in the coconut oil and corn oil groups (1.5- 1.2 fold, respectively). TNF-alpha mRNA accumulation in the fish oil group was not due to increased stability of mRNA and protein synthesis was not involved in this phenomenon. The authors discussed the mechanisms by which fish oil could increase TNF-alpha production by LPS stimulated macrophages.