Effects of orally administered retinol on natural killer cell activity in wild type BALB/c and congenitally athymic BALB/c mice.
Retinoids have been shown to inhibit the growth and development of neoplastic cells in many systems. One mechanism of action may be through activation of the immune system, specifically natural killer (NK) cell activity. The effect of retinol on NK cell cytotoxicity was examined in three groups of mice: BALB/c (wild-type), BALB/c nu/nu (athymic), and BALB/c nu/nu previously injected with human tumor cells. In untreated mice, NK activity was highest in athymic mice without tumors and lowest in wild-type mice, although serum and liver retinol concentrations were identical in all three groups. In mice fed graded, nontoxic doses of retinol daily for 3 weeks, serum retinol levels in all three groups exhibited a sharp peak and decline following daily bolus retinol administration. Retinol stores in the livers showed a dose-dependent increase in all treated animals. However, NK cell activity, differed for each group. Athymic mice without tumors exhibited no change in NK activity as a result of retinol treatment. Athymic mice with tumors had NK levels that tended to increase with increasing retinol doses, but these changes were not statistically significant. Wild-type mice, on the other hand, demonstrated significantly higher NK levels after treatment with retinol doses of 300 and 600 micrograms/day. In subsequent time course experiments, there was a peak in NK activity 1 h following bolus retinol administration similar to the peak seen in serum retinol concentrations, suggesting either an acute activation or recruitment of cytotoxic cells. Retinol thus appears to increase NK activity in wild-type BALB/c mice, and this activity may be an important component of its antineoplastic activity.
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology*; D008819:Mice, Nude / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014801:Vitamin A / Q000378:metabolism / Q000494:pharmacology*
D014801:Vitamin A