ESSENTIAL FATTY-ACID DEFICIENCY PREVENTS AUTOIMMUNE DIABETES IN NONOBESE DIABETIC MICE THROUGH A POSITIVE IMPACT ON ANTIGEN-PRESENTING CELLS AND TH2 LYMPHOCYTES

Protective effects of essential fatty acid deficiency (EFAD) on autoim munity were shown in rodents. Our goal was to investigate the mechanis ms of EFAD effects on autoimmune diabetes in nonobese diabetic (NOD) m ice. Weanling female mice were randomized between a control diet group and an EFAD diet group, and the development of diabetes and immune re sponse was determined over a 6-month period. The cumulative incidence of diabetes was significantly reduced in the EFAD group (20 vs 68.75% in the control group; p < 0.01), without affecting the insulitis proce ss. Splenocyte reactivity to phytohemagglutinin and anti-CD3 antibody was significantly increased in EFAD-fed mice ( p < 0.01). The EFAD gro up also exhibited a dramatic increase in baseline (29-fold) and antige n-presenting cell (APC)-stimulated (10-fold) T cell responses in synge neic mixed leukocyte reaction. These responses were associated with a marked increase in splenocyte interleukin-4 (IL-4) production, a reduc tion in interferon-gamma production, and a down-regulation of CD45RB i soform expression. Macrophages in the EFAD group exerted a reduced sup pressive effect on concanavalin A-induced splenocyte proliferation and were found to release increased amounts of tumor necrosis factor-alph a and IL-1 and reduced amounts of prostaglandin E(2). These results cl early demonstrate that EFAD prevents diabetes in NOD mice. The data su ggest an enhanced activity of Th2-like cells, as well as an effect on APC activity linked to alteration in eicosanoid metabolism.