Chronic marginal vitamin A status reduces natural killer cell number and function in aging Lewis rats

Natural killer (NK) cells function in the regulation of immune responses and in the surveillance of malignant or other abnormal cells. Little is known of the effects of chronic marginal vitamin A (VA) status or VA supplementation, or their interaction with age, on NK cell number and cytolytic activity. We have conducted a two-factor (diet, age) study in which male Lewis rats were fed AIN-93M diet, modified to contain either 0.3 (designated marginal), 4.0 (control) or 50 (supplemented) mg retinol equivalents (RE)/kg diet, from the time of weaning until the ages of 2.5 mo (young), 8-10 mo (middle-aged) or 18-20 mo (old). Natural killer cells were identified and quantified in peripheral blood mononuclear cells (PBMC) and spleen with the use of flow cytometry, and NK cell cytotoxicity was assayed. The number and percentage of PBMC NK cells increased with age (P < 0.0001 by two-way ANOVA). For all age groups, values were lowest in rats with marginal VA status (P < 0.0001 vs. controls). NK cell lytic activity also declined with age (P = 0. 0003). As a result, NK cell lytic efficiency (lytic activity per NK cell) decreased markedly with age (P < 0.0001). Regardless of the donor's age or VA status, PBMC NK cell cytotoxicity doubled (100 +/- 25% increase) after exposure to interferon-alpha (5 x 10(5) U/L for 1 h before assay), indicating that IFN-stimulated lytic activity was related directly to basal NK cell activity. If the relationships observed in this animal model can be applied to humans, these data suggest that elderly people consuming diets chronically low in VA may be at increased risk for infectious or neoplastic diseases.