Beneficial effect of an essential fatty acid deficient diet in NZB/NZW F1 mice

Abstract

New Zealand Black by White (B/W) hybrid mice spontaneously develop a disease similar to systemic lupus erythematosus (SLE). Subepidermal immunoglobulin deposits (Se-Ig) and antibodies to double-stranded DNA (anti-dsDNA) develop in aging mice. Death from glomerulonephritis occurs at 8 to 12 mo. Previous findings suggest that epidermal DNA:anti-dsDNA complexes form in situ since Se-Ig correlates with anti-ds DNA and Se-Ig accumulation is augmented by increased epidermal proliferation (presumably due to enhanced epidermal DNA release). Since essential fatty acid (EFA) deficiency is known to increase epidermal proliferation we have studied the effect of an essential fatty acid deficient EFA-d diet on: (1) Se-Ig, anti-dsDNA, and (3) survival. Ten-mo B/W mice on an EFA-d diet were compared with 14 controls on a calorically equivalent standard diet. Both groups were initiated on their diets at 2 mo of age. Only female mice were used. All were weighed weekly; tested for anti-ds DNA (Crithidia luciliae assay) each month; and biopsied for direct immunofluorescence (IF) staining of skin at 6, 7.5, 9, 10.5, and 12 mo. Tissue (skin and kidney) was also obtained for light and IF microscopy. Weights in the 2 study groups were essentially identical. All disease manifestations examined were strikingly altered in the EFA-d animals. Only 2 of 14 (14%) control animals survived to 9 mo and both had anti-dsDNA and Se-Ig. In contrast, 8 of 10 (80%) EFA-d mice were alive at 9 mo and none had anti-dsDNA or Se-Ig. The kidneys from EFA-d mice at 10 mo were normal; however, all kidneys from 7 to 9 mo control mice were abnormal by both light and IF microscopy. Eight of the 10 EFA-d mice were alive at 10 mo. None had Se-Ig but one had anti-dsDNA. At 16 mo (4 mo after controls had died) 7 of 10 EFA-d mice were living and 60% were anti-ds DNA positive. These findings strongly suggest that (1) SE-Ig is present in mice with anti-dsDNA and severe renal disease and (2) EFA-d produces a profoundly beneficial effect in the disease process.