| Epidemiologic studies, supported by human intervention trials, indicate that frequent nut consumption can make a significant contribution to reducing the risk of heart disease. However, approximately 0.7% of the US population reports IgE-mediated allergic reactions upon ingestion of tree nuts, with walnut the most commonly implicated tree nut. English walnuts ( Juglans regia) are not only a good source of polyunsaturated fatty acids (PUFA), but also antioxidants (polyphenolics and tocopherols); each of these constituents as a general class of macro- and micronutrients has been shown to modulate a variety of immune functions. Our objectives were to investigate the anti-atherogenic effects of walnut polyphenolics and to examine the association between food allergy and walnut kernel polyphenolics (in vitro) and walnut consumption by human subjects ( in vivo ex vivo). Walnut polyphenolics, extracts and purified ellagic acid (EA), demonstrated an ability to inhibit in vitro plasma and LDL oxidation that was induced by metal ions (copper) and a free radical generator, 2,2′-azobis′(2-amidino propane) hydrochloride (AAPH). In vitro stimulated (PHA, α-CD3 and PMA/Ionomycin) peripheral blood mononuclear cells (PBMC) proliferation and Th2 (IL-13 and TNF-α) cytokine production from PHA-stimulated PBMC was inhibited in response to walnut polyphenolics. Paradoxically, IL-2 increased and IL-4 remained unchanged. To investigate effects on cells previously stimulated by PHA, a time course experiment was conducted. When added at time 0 minutes and 2 hours, EA dose-dependently inhibited PHA-induced proliferation. However, at 30 minutes and 1 hour, low doses of EA (10 and 1 μM) significantly increased proliferation above that of PHA. Long-term consumption of walnuts by obese (BMI = 33.8 ± 2.1 SEM) women diagnosed with polycystic ovarian syndrome (PCOS) resulted in increased proliferation and cytokine production (IL-2, IL-4, IL-13 and TNF-α) and expression (IL-4) from ex vivo PHA-stimulated PBMC. No change in IL-1β production, IFN-γ and TGF-β expression or circulating IgE levels was observed. In conclusion, the anti-atherogenic properties of walnuts were supported; in vitro, our data did not support the hypothesis that walnut polyphenolics skew a cytokine response towards Th2, however, walnut consumption did support this hypothesis by demonstrating immunostimulatory effects towards Th2 and ex vivo stimulated PBMC proliferation. |
