Reduced IL‐10 production contributes to impaired NK cytotoxicity in old mice fed a high folic acid diet (638.3)

Abstract

Natural killer (NK) cells are important for immunity against malignant and virally infected cells. High folic acid intake, which may be linked with higher risk of colon cancer, was associated with lower NK activity in older women. To study the underlying mechanisms, we created a mouse model and found that aged mice fed a high folic acid (HFA) diet had reduced NK activity. In this study, we determined if expression of cytokines that are known to activate NK activity (IL‐10, IFN‐γ, TNF‐α) are affected by a HFA diet in aged mice.Female C57BL/6 mice (16 mo) were fed a control (1x RDA folic acid) or a HFA diet (20x RDA folic acid) for 3 months. Splenocytes were collected and stimulated with LPS for 24 h for ex vivo production of IL‐10, IFN‐γ, and TNF‐α determined by cytometric bead array.In HFA mice, IL‐10 production was 50.7% less than that of the control mice (P=0.028) but no differences were found in IFN‐γ and TNF‐α production. Since IL‐10 activates NK cells, we examined whether addition of IL‐10 to the splenocyte cultures would restore NK activity in the HFA group. We found that NK activity increased for both groups (P<0.01), but the HFA group had larger percent increase in NK activity as compared to control mice (P=0.058). These results indicate that IL‐10 restored the lower NK activity in aged mice fed a HFA diet.These findings suggest the decreased NK activity due to a high folic acid diet may in part be due to impaired IL‐10 secretion.Grant Funding Source: Supported by USDA contract # 51520‐008‐045 and HNRCA Pilot grant