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 i nterleukin-12 (IL-12) and interferon-gamma (IFN gamma) production during th e early stage of an infectious challenge with Listeria monocytogenes. Weanl ing 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 w eeks, mice were injected intraperitoneally with 10(5) Listeria monocytogene s and the concentration of IL-12(p70) and IFN gamma in serum was determined 24 h post-infection by ELISA. IL-12p35, IL-12p40 mRNA, and IFN gamma mRNA in the spleen were quantified by RNase protection assay. The number of IFN gamma-producing cells in the spleen was determined by flow cytometry using an intracellular staining procedure. We found that n-3 PUFA-fed mice had lo wer levels of circulating IL-12 at 24 h post-infection than n-6 PUFA- or lo w 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 n ot significantly differ among dietary treatment groups. However, IL-12p40 m RNA 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 circulat ing IFN gamma (4.4 +/- 1.8 ng/ml vs. 9.1 +/- 1.0, and 9.7 +/- 2.1 ng/ml, re spectively; P = 0.007, n = g-10/trt). The n-3 PUFA-fed mice had significant ly lower IFN gamma mRNA in their spleens compared to the mice fed the other fat sources, In agreement with having lower circulating IFN gamma and lowe r splenic IFN gamma mRNA, n-3 PUFA-fed mice had a significantly lower perce ntage of IFN gamma-producing cells in their spleens compared with the n-6 P UFA-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 IFN gamma during the early phase of a List eria infection. (C) 1999 Elsevier Science B.V. All rights reserved.