Dietary Omega-3 Polyunsaturated Fatty Acids from Fish Oil Reduce Interleukin-12 and Interferon-gamma Production in Mice

The objective of this study was to investigate the impact of feeding mice a diet rich in n-3 polyunsaturated fatty acids (PUFA) from fish oil on the interleukin-12 (IL-12) and interferon-gamma (IFNgamma) production during the early stage of an infectious challenge with Listeria monocytogenes. Weanling female C3H/HeN mice were fed AIN-93G experimental diets containing 20%, by weight one of three fat sources: lard (low PUFA), soybean oil (n-6 PUFA) or a mixture (9:1) of menhaden fish oil and corn oil (n-3 PUFA). After 4 weeks, mice were injected intraperitoneally with 10(5) Listeria monocytogenes and the concentration of IL-12(p70) and IFNgamma in serum was determined 24 h post-infection by ELISA. IL-12p35, IL-12p40 mRNA, and IFNgamma mRNA in the spleen were quantified by RNase protection assay. The number of IFNgamma-producing cells in the spleen was determined by flow cytometry using an intracellular staining procedure. We found that n-3 PUFA-fed mice had lower levels of circulating IL-12 at 24 h post-infection than n-6 PUFA- or low PUFA-fed mice (9.7+/-3.4 pg/ml vs. 61.6+/-10.6, and 44.4+/-12.5 pg/ml, respectively; P=0.002, n = 10/trt). The level of IL-12 p35 mRNA did not significantly differ among dietary treatment groups. However, IL-12p40 mRNA was significantly lower in n-3 PUFA- and n-6 PUFA-fed mice compared to low-PUFA-fed mice. Further, the n-3 PUFA group also had the lowest circulating IFNgamma (4.4+/-1.8 ng/ml vs. 9.1+/-1.0, and 9.7+/-2.1 ng/ml, respectively; P = 0.007. n = 8-10/trt). The n-3 PUFA-fed mice had significantly lower IFNgamma mRNA in their spleens compared to the mice fed the other fat sources. In agreement with having lower circulating IFNgamma and lower splenic IFNgamma mRNA, n-3 PUFA-fed mice had a significantly lower percentage of IFNgamma-producing cells in their spleens compared with the n-6 PUFA-fed group (2.1+/-0.6 vs. 4.2+/-0.7%; P = 0.037, n = 10/trt). In summary, feeding mice a diet rich in n-3 PUFA from fish oil significantly lowered the production of both IL-12 and IFNgamma during the early phase of a Listeria infection.