1338 Dietary Fish Oil and Arthritis in Mice

The prolonged bleeding times (1) and protection against thrombosis found in Eskimos (2) is thought to be related to a marine diet rich in c0-3-fatty acids (3). Recently, fish oil diets have been shown to modify the course of rheumatoid arthritis (4). In animal models of disease, diet enrichment with eicosapentaenoic acid (EPA), ~ an c0-3-fatty acid present in fish oil, protected the NZB/NZW mouse from glomerular nephritis (5), though augment ing susceptibility of rats to type II col lagen-induced arthritis (CIA) (6). CIA is suspected of being immunologically mediated, in that anticollagen antibodies seem to be a necessary, if not sufficient, requirement for disease induction (7). Antigenic recognition of collagen, and amplification of the response requires a complex interplay of chemical signals and cell-cell interactions (8). Evidence is accumulating that prostaglandins (PG) are among such intercellular mediators operating at several levels of the response (9). Macrophages, besides initiating the immune response, also produce large quantities of PG (10, 1 1), and are unique in that they contain high levels of esterified arachidonic acid (AA) (12), the most abundant of the PG precursors. We have examined the changes taking place in this precursor pool and the resulting PG profile when arthritis-susceptible mice are fed a diet enriched with EPA, a less common PG precursor. We find that this diet produces marked enrichment of ¢0-3-fatty acids in macrophage phospholipids, depresses production of PG of the 2 series, and decreases mouse susceptibility to CIA.