The oxidant-antioxidant balance is an important determinant of immune cell function, including maintaining the integrity and functionality of membrane lipids, cellular proteins, and nucleic acids and controlling signal transduction and gene expression in immune cells. Optimal amounts of antioxidants are needed for maintenance of the immune response across all age groups. This need might be more critical, however, in aged persons. Age-associated dysregulation of immune response, particularly of T cell-mediated function, is well documented. The well-known age-related increase in free radical formation and lipid peroxidation contributes, at least in part, to this phenomenon. We summarize animal and human studies undertaken by ourselves as well as other investigators on the effects of antioxidants, vitamin E, beta-carotene, and glutathione on the immune response of aged persons. The underlying mechanisms for the antioxidant nutrients' effects as well as their health implications for aged persons are discussed.

Aging is associated with a decline in the immune response in mammals. Conjugated linoleic acid (CLA) has been suggested to have immunoenhancing properties. We examined the influence of dietary CLA on the immune response of young and old mice. Forty young (4 mo) and 40 old (22 mo) mice consumed ad libitum diets containing 0 or 1 g CLA /100 g for 8 wk. Splenocytes from half of the mice were isolated to evaluate proliferation to concanavalin A (Con A) (0.5, 1.5, 5.0 mg/L) and phytohemagglutinin A (PHA) (5, 20, 40 mg/L) and lipopolysaccharide (LPS) (5, 15, 30 mg/L), natural killer cell (NK) activity and prostaglandin (PG)E2 and interleukin (IL)-2 production. The remaining mice were used to evaluate in vivo delayed-type hypersensitivity (DTH) skin response. There was a significant decline due to age in response to all three mitogens tested (P < 0. 05). CLA supplementation significantly increased all CLA isomers measured in hepatic neutral lipids and phospholipids (P < 0.05). Young mice fed 1% CLA had greater splenocyte proliferation in response to Con A (0.5 and 5.0 mg/L) and PHA (40 mg/L) (P < 0.05) than young mice fed control diet. Old mice fed 1 g CLA/100 g had significantly higher proliferative response to optimal concentrations of Con A (1.5 mg/L) (P < 0.001) than the mice fed the control diet. Old mice fed the control diet had significantly lower splenocyte IL-2 production than the young mice (P < 0.005). CLA-supplemented young mice had significantly higher splenocyte IL-2 production than those fed the control diet (P < 0.05). CLA had no effect on NK cell activity, PGE2 production or DTH in young or old mice. Further studies are needed to determine the mechanism of CLA-induced enhancement of IL-2 production and T cell proliferation.

Ileal proglucagon gene expression and postprandial plasma concentrations of proglucagon-derived peptides are reported to change with the type and quantity of dietary fiber ingested by rats. Within the intestine, proglucagon encodes several proglucagon-derived peptides known to modulate intestinal absorption capacity and pancreatic insulin secretion. To determine whether the chronic ingestion of fermentable dietary fiber regulates the expression and synthesis of proglucagon-derived peptides in the distal intestine to modulate glucose homeostasis, the following study was conducted: 16 adult dogs (23 +/- 2 kg) were fed isoenergetic, isonitrogenous diets containing a mixture of high fermentable dietary fibers (HFF) or low fermentable (LFF) wood cellulose for 14 d in a randomized cross-over design. Food was withheld for 16 h before an oral glucose tolerance test was conducted supplying 2 g of glucose/kg body wt, and peripheral blood was collected via a hind-leg catheter at 0, 15, 30, 45, 60, 90 and 120 min for plasma glucose, insulin and glucagon-like peptide-1(7-36)NH2 (GLP-1) analyses. Intestinal samples were collected after the second dietary treatment. Ileal proglucagon mRNA, intestinal (GLP-1) concentrations and the integrated area under the curves (AUC) for plasma GLP-1 and insulin were greater and plasma glucose AUC was reduced when dogs were fed the HFF diet compared to the LFF diet (P < 0.05). Intestinal villi heights, brush border and basolateral glucose transporter protein abundance and jejunal transport capacities were significantly greater when dogs were fed the HFF diet than when fed the LFF diet. In conclusion, improvements in glucose homeostasis are observed in healthy dogs when they ingest fermentable fibers.

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Effects of vitamin E (E) supplementation on influenza infection were examined in young and old C57BL/6NIA mice fed 30 or 500 ppm of E for 6 weeks and subsequently infected with influenza A/Port Chalmers/1/73 (H3N2). Old mice fed 30 ppm of E had significantly higher lung virus titers on days 2 and 7 after infection than young mice fed 30 ppm of E. Titers on all 3 days were significantly lower in old mice fed 500 ppm of E than in those fed 30 ppm. Significant effects of E on lung virus titers in young mice were observed on only day 5, but E caused more reduction of virus titers in old than in young mice (25-fold vs. 15-fold). An age-associated decline in NK cell activity was restored by 500 ppm of E in old but not young mice. Pulmonary cytotoxic T lymphocyte activity on day 7 was not affected by age or E. These experiments demonstrate that high doses of E significantly enhance influenza viral clearance in aged mice but only modestly affect young mice.

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