Enhancement of natural killer-cell activity in young and old mice treated with cyclophosphamide on a circadian basis

Several recent studies have revealed a significant circadian variation in immunological functions including natural killer (NK)-cell activity against tumor target cells both in rodents and in man. We have previously reported circadian changes in antibody-forming cells as well as NK-cell activity in mice and rats. The present study was undertaken to determine the effect of high and low doses of cyclophosphamide on circadian NK-cell activity in young (8-week-old) and old (8-month-old) female C57BL/6 (B/6) mice. The results revealed that, in general, young animals had higher NK activity than old animals. In both young and old mice, the high dose of cyclophosphamide depressed NK activity. In contrast, the low dose of cyclophosphamide showed significantly increased NK activity, which was proportionately greater in old mice than in young mice. Cyclophosphamide-enhanced NK activity was found to be higher during the resting period than during periods of activity. Apparently, high NK activity can be induced with a circadian-based immunotherapy regime using low-dose cyclophosphamide in both young and old animals. It is presently not clear if increased NK activity caused by cyclophosphamide is due to a decrease in activity of immunoregulatory cells, such as T cells, B cells, or macrophages. More studies are required to determine the basis of increased NK activity caused by treatment with low dosages of cyclophosphamide in mice.