No abstract

Although essential to host defense, neutrophils are also involved in numerous inflammatory disorders including rheumatoid arthritis. Dietary supplementation with relatively large amounts of fish oil [containing >2.6 g eicosapentaenoic acid (EPA) plus 1.4 g docosahexaenoic acid (DHA) per day] can attenuate neutrophil functions such as chemotaxis and superoxide radical production. In this study, the effects of more moderate supplementation with fish oil on neutrophil lipid composition and function were investigated. The rationale for using lower supplementary doses of fish oil was to avoid adverse gastrointestinal problems, which have been observed at high supplementary concentrations of fish oil. Healthy male volunteers aged <40 yr were randomly assigned to consume one of six dietary supplements daily for 12 wk (n = 8 per treatment group). The dietary supplements included four different concentrations of fish oil (the most concentrated fish oil provided 0.58 g EPA plus 1.67 g DHA per day), linseed oil, and a placebo oil. The percentages of EPA and DHA increased (both P < 0.05) in neutrophil phospholipids in a dose-dependent manner after 4 wk of supplementation with the three most concentrated fish oil supplements. No further increases in EPA or DHA levels were observed after 4 wk. The percentage of arachidonic acid in neutrophil phospholipids decreased (P < 0.05) after 12 wk supplementation with the linseed oil supplement or the two most concentrated fish oil supplements. There were no significant changes in N-formyl-met-leu-phe-induced chemotaxis and superoxide radical production following the dietary supplementations. In conclusion, low-to-moderate amounts of dietary fish oil can be used to manipulate neutrophil fatty acid composition. However, this may not be accompanied by modulation of neutrophil functions such as chemotaxis and superoxide radical production.

Eleven mammalian toll-like receptors (TLRs 1-11) have been identified to date and are known to play a crucial role in the regulation of immune responses; however, the factors that regulate TLR expression and function in vivo are poorly understood. Therefore, in the present study, we investigated the physiological regulation of TLR expression and function in humans. To examine the influence of diurnal rhythmicity on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers (n = 8) at time points coinciding with the peak and nadir in the endogenous circulating cortisol concentration. While no diurnal rhythmicity in the expression of TLRs 1, 2, 4 or 9 was observed, the upregulation of costimulatory (CD80 and CD86) and antigen-presenting (MHC class II) molecules on CD14 + monocytes following activation with specific TLR ligands was greater (P < 0.05) in samples obtained in the evening compared with the morning. To examine the influence of physical stress on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers (n = 11) at rest and following 1.5 h of strenuous exercise in the heat (34 • C). Strenuous exercise resulted in a decrease (P < 0.005) in the expression of TLRs 1, 2 and 4 on CD14 + monocytes. Furthermore, the upregulation of CD80, CD86, MHC class II and interleukin-6 by CD14 + monocytes following activation with specific TLR ligands was decreased (P < 0.05) in samples obtained following exercise compared with at rest. These results demonstrate that TLR function is subject to modulation under physiological conditions in vivo and provide evidence for the role of immunomodulatory hormones in the regulation of TLR function.

No abstract

To investigate the effect of dietary lipids with different fatty acid compositions upon the in vivo cytokine response to bacterial lipopolysaccharide (LPS), mice were fed for 5 weeks on a low-fat diet or on one of four high-fat diets that contained 20%, by weight, of coconut oil (CO), olive oil (OO), safflower oil (SO) or fish oil (FO). The mice were injected intraperitoneally with a non-lethal dose of Escherichia coli LPS (100 micrograms/20 g body weight) and killed 90 or 180 min later. Plasma tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1alpha, IL-6 and IL-10 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Plasma TNF-alpha and IL-10 concentrations were higher 90 min postinjection than after 180 min, whereas plasma IL-1beta and IL-6 concentrations were higher 180 min postinjection than after 90 min. Peak plasma TNF-alpha, IL-1beta and IL-6 concentrations were lower in the CO- and FO-fed mice than in those fed the SO diet. Peak plasma IL-10 concentrations were higher in CO-fed mice than in those fed some of the other diets. These observations suggest that, relative to the n-6 polyunsaturated fatty acid-rich SO diet, CO and FO diminish production of proinflammatory cytokines in vivo. This indicates that these fatty acids might be useful therapies in acute and chronic inflammatory diseases. The enhanced production of IL-10 following CO feeding appears to be an additional antiinflammatory effect of this oil, which could give added benefit in various clinical conditions.