n-3 Polyunsaturated fatty acids and autoimmune-mediated glomerulonephritis

Abstract 

Consumption of n-3 polyunsaturated fatty acids (PUFAs) found in fish oil suppresses inflammatory processes making these fatty acids attractive candidates for both the prevention and amelioration of several organ-specific and systemic autoimmune diseases. Both pre-clinical and clinical studies have been conducted to determine whether fish oils containing the n-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) can be used in the prevention and treatment of immunoglobulin A nephropathy (IgAN) and lupus nephritis. In a toxin-induced mouse model that mimics the early stages of IgAN, n-3 PUFA consumption suppresses aberrant interleukin (IL)-6-driven IgA production and mesangial IgA immune complex deposition by impairing phosphorylation of upstream kinases and activation of transcription factors essential for IL-6 gene transcription. n-3 PUFAs can also suppress production of anti-double-stranded DNA IgG antibodies and the resultant development of lupus nephritis in the NZBW F1 mouse and related models. These effects have been linked in part to impaired expression of proinflammatory cytokines and adhesion molecules as well as increases in antioxidant enzymes in kidney and immune organs. Several recent clinical trials have provided compelling evidence that n-3 PUFA supplementation could be useful in treatment of human IgAN and lupus nephritis, although some other studies suggest such supplementation might be without benefit. Future investigations employing genomics/proteomics and novel genetically altered mice should provide further insight into how n-3 PUFAs modulate these diseases as well help to identify clinically relevant biomarkers. The latter could be employed in future well-designed, long-term clinical studies that will resolve current controversies on n-3 PUFA efficacy in autoimmune-mediated glomerulonephritis.

Abbreviations: PUFAs, polyunsaturated fatty acids, DHA, docosahexaenoic acid, EPA, eicosapentaenoic acid, IgAN, immunoglobulin A nephropathy, PGs, prostaglandins, LTs, leukotrienes, COX, cyclooxygenase, ESRD, end-stage renal disease, CKD, chronic kidney disease, SLE, systemic lupus erythematosus, DON, deoxynivalenol, CREB, cAMP response element binding, C/EPBβ, CCAAT/enhancer binding protein β, NF-κB, nuclear factor κB, IC, immune complexes, hnRNA, heteronuclear nuclear RNA, PKR, RNA-activated protein kinase, AA, arachidonic acid, HSP, Henoch-Schonlein purpura, SLE, systemic lupus erythmatosus, NZBW F1, New Zealand Black White (F1) mouse, BXSB, C57BL/6 x satin beige mice, DHA-E, DHA ethyl ester, EPA-E, EPA ethyl ester, SLAM-R, Systemic lupus activity measure