The Journal of Nutrition
Dietary Fish Oil Increases the Number of Splenic
Macrophages Secreting TNF-a and IL-10 But
Decreases the Secretion of These Cytokines by
Splenic T Cells from Mice1,2
Dagbjort H. Petursdottir and Ingibjorg Hardardottir*
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland
Dietary fish oil has immunomodulatory effects that are partly mediated by its effects on cytokine secretion. In this paper,
we examine whether dietary fish oil has different effects on cytokine secretion by T cells and macrophages. Female BalbC
mice were fed diets supplemented with 18% fish oil 1 2% corn oil or 20% corn oil. Concanavalin A (ConA)- and LPS-
induced TNF-a and IL-10 secretion by splenocytes was examined using ELISA. Dietary fish oil decreased ConA induced-,
butincreasedLPS-induced, TNF-aand IL-10secretionbytotalmurinesplenocytes.Dietaryfishoilincreasedthenumberof
splenocytes secreting TNF-a and IL-10, following stimulation with LPS, by 123 and 38%, respectively, but did not affect
cytokine secretion by each cell, as determined using enzyme-linked immunospot. Spleens from mice fed the fish oil diet
had over 2-fold higher proportion of macrophages with high expression of CD11b than spleens from mice fed the corn
oil diet. In addition, fish oil increased the proportion of total and CD11b1splenocytes that expressed the LPS receptor
complex molecules, CD14 and toll-like receptor (TLR)4/myeloid differentiation factor-2 (MD-2), by 85 and 28%, respec-
tively. The increased proportion of macrophages expressing the LPS receptor complex molecules, CD14 and TLR4/MD-2,
in spleens from mice fed the fish oil diet may explain the increased number of cells that secreted the cytokines after LPS
stimulation.J. Nutr. 137: 665–670, 2007.
The immunomodulatory effects of dietary fish oil are generally
thought to be antiinflammatory (1). This hypothesis is based on
results from human studies indicating that dietary fish oil or
(n-3) PUFA arebeneficial inseveralinflammatory disorders (2–4).
The antiinflammatory effects of dietary fish oil are thought to be
mediated in part by decreased proinflammatory cytokine pro-
duction, shown, for example, by decreased circulating IL-1b
levels in patients with rheumatoid arthritis (5) and decreased
LPS-induced TNF-a and IL-1b secretion by human peripheral
blood mononuclear cells (6–8). Decreased IL-2 secretion by
murine T lymphocytes stimulated with concanavalin A (ConA)3
or anti-CD3/anti-CD28 (9,10) has also been shown following
feeding with low- (5 g/100 g) or high- (18 g/100 g) fat diets
containing (n-3) PUFA or fish oil (9–11). In addition, a number
of studies have shown that dietary fish oil, or (n-3) PUFA, de-
crease mitogen-induced proliferation by lymphocytes in rodents
and men fed low- or high-fat diets (7,10,12–16). The decreased
lymphoproliferation may be dependent on dietary fish oil mod-
ification of lipid rafts and displacement of signaling proteins and
cytokine receptors from lipid rafts (17,18). Displacement of
signaling proteins and cytokine receptors from lipid rafts could
lead to decreased intracellular signaling and dietary fish oil has
indeed been shown to decrease events linked to intracellular
signaling, such as formation of diacylglycerol and ceramide (10),
tyrosine phosphorylation of protein kinase C-g (19), and recruit-
ment of protein kinase C-u to lipid rafts (9).
Although dietary fish oil has antiinflammatory effects on
cytokine secretion by circulating monocytes and T cells, as de-
scribed above, results from several studies show that dietary fish
oil has proinflammatory effects on cytokine secretion by macro-
phages. We and others have shown that feeding mice fish oil
increases LPS-induced TNF-a and IL-1b secretion by resident
peritoneal macrophages (20–27) but decreases secretion of the
antiinflammatory cytokine, IL-10 (25). In addition, dietary fish
oil increases TNF-a secretion by murine splenocytes after stimu-
lation with LPS (28,29). These proinflammatory effects were
seen in mice fed diets containing 5 (29), 10 (22–24,26), or 20
g/100 g fat (25), with (n-3) PUFA being as low as 1.5 g/100 g in
one of these studies (22). The increased TNF-a secretion by
resident peritoneal macrophages from mice fed fish oil is partly
1Supported by a grant from the Icelandic Research Council’s Research Fund and
Graduate Education Fund (DHP) and The Research Fund of the University of
2Supplemental Tables 1 and 2 and Supplemental Figure 1 are available with the
online posting of this paper at jn.nutrition.org.
3Abbreviations used: ConA, concanavalin A; ELISpot, enzyme-linked immuno-
spot; MD-2, myeloid differentiation factor-2; TLR, toll-like receptor.
* To whom correspondence should be addressed. E-mail: firstname.lastname@example.org.
0022-3166/07 $8.00 ª 2007 American Society for Nutrition.
Manuscript received 22 September 2006. Initial review completed 6 November 2006. Revision accepted 10 December 2006.
by guest on June 6, 2013
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