It is recognised that polymorphisms in the apolipoprotein (APO)E (epsilon) gene play an important role in cardiovascular disease (CVD) risk( 1 ). In addition to modestly higher plasma cholesterol, a pro-inflammatory phenotype has been reported in carriers of the APOE4 allele( 2 ). Our aim was to explore the impact of chronic dietary fat manipulation on cytokines production according to APOE genotype.
Fifty two healthy participants (mean age 50 (sd 9) y and BMI 26.4 (sd 4.3) kg/m2) were prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4), and assigned to three iso-energetic diets; low fat (LF, 24% energy (E) from fat, 8%E saturated fat (SFA)), high fat-high saturated fat (HSF, 38%E fat, 18%E SFA), and HSF with 3 g/d docosahexaenoic (HSF-DHA) diets, each for an 8-wk period in a sequential design. Fasting blood samples were collected at baseline and at the end of each of the intervention diets. Concentrations of interleukin (IL)-1 β, IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)-α were measured in cell free supernatants derived from whole blood culture assays stimulated for 24 h with either 0.05 or 1 μg/ml of bacterial lipopolysaccharide (LPS), using a cytokine multiplex antibody bead kit (Invitrogen)( 3 ). Cytokine production was corrected for the number of monocytes in the whole blood cultures.
Effect of dietary fat manipulation on cytokine production (pg per 103 monocytes) by 0.05 μg/ml LPS-stimulated whole blood cultures of fifty two healthy subjects. NS, not significant. a,bMean values within a row with unlike superscript letters were significantly different (P⩽0.05).
No diet*genotype interactions were found, although a significant diet interaction was observed for TNF-α and IL-10 production after stimulation with 0.05 μg/ml LPS (P=0.012 and P=0.036 respectively) and 1 μg/ml LPS (P=0.006, P=0.049). TNF-α concentrations were higher (P⩽0.05) after the HSF diet compared with the baseline, whereas IL-10 was higher (P⩽0.05) after the LF diet compared with the baseline and HSF-DHA diet. Our study data suggests a greater sensitivity of monocyte cytokine production to the quality and quantity of dietary fat, than APOE genotype in healthy participants.