Severe folate deficiency impairs natural killer cell-mediated cytotoxicity in rats

Abstract

Dietary folate deficiency enhances, whereas folate supplementation suppresses, the development of several cancers. This study investigated the effect of folate deficiency on natural killer cell (NK)-mediated cytotoxicity, which is important in immune surveillance against tumor cells. In Experiment 1, severe folate deficiency was induced in rats by feeding an amino acid-defined diet containing 0 mg folate and 10 g succinylsulfathiazole/kg diet. Control and folate-supplemented rats were fed the same diet containing 2 (basal requirement) and 8 mg folate/kg diet, respectively. Severe folate deficiency at the end of wk 5 was associated with 20% growth retardation, a 60% reduction in lymphocyte counts and significantly impaired NK-mediated cytotoxicity compared with the control and folate-supplemented groups (P < 0.02). The lesser degree of severe folate deficiency achieved by wk 4 was not associated with impaired NK-mediated cytotoxicity. Folate supplementation at 4× the basal requirement did not significantly enhance NK-mediated cytotoxicity at either time point. In Experiment 2, moderate folate deficiency was induced in rats by feeding the same diet without succinylsulfathiazole. NK-mediated cytotoxicity in the moderately folate-deficient rats (without growth retardation or lymphopenia) was not significantly different from that in controls. Although severe folate deficiency may have adverse effects on NK-mediated cytotoxicity, moderate folate deficiency, a degree of depletion associated with an increased risk of several cancers, appears not to affect NK-mediated cytotoxicity in rats. Furthermore, a modest level of folate supplementation above the basal requirement does not enhance NK-mediated cytotoxicity. These data collectively suggest that NK-mediated cytotoxicity is not a likely mechanism by which folate status modulates carcinogenesis.