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 an d, in the surveillance of malignant or other abnormal cells. Little is know n of the effects of chronic marginal vitamin A (VA) status or VA supplement ation, or their interaction with age, on NK cell number and: cytolytic acti vity. 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 marg inal), 4.0 (control) or 50 (supplemented) mg retinol equivalents (RE)/kg di et, from the time of weaning until the ages of 2.5 mo (young), 8-10 mo (mid dle-aged) or 18-20 mo (old). Natural killer cells were identified and quant ified in peripheral blood mononuclear cells (PBMC) and spleen with the use of flow cytometry, and NK cell cytotoxicity was assayed. The number and per centage 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 e xposure to interferon-alpha (5 x 10(5) u/L for 1 h before assay), indicatin g 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 chronica lly low in VA may be at increased risk for infectious or neoplastic disease s.