Depressed natural killer and lectin-induced cell-mediated cytotoxicity in cholesterol-fed guinea pigs

Dunkin-Hartley and Hartley guinea pigs were fed a diet containing 1% cholesterol (C+) or a control diet (C-). The C+-fed guinea pigs showed a decrease in antitumor effector cell levels as measured by an in vitro 18-hour 51Cr release assay. Natural killer (NK) activity fell rapidly after initiation of cholesterol feeding, decreasing to 25.6% of control levels by 2 weeks. While the interferon inducer polyinosinic-polycytidylic acid increased NK activity as much as 3.6-fold in controls, the NK levels in C+-fed animals were not increased. NK activity was lower in both spleen and peripheral blood of C+-fed animals and against K562, MOLT-3, HL-60, and Raji target cells. Lectin-dependent cell-mediated cytotoxicity was increased in the C+-fed group over, the first 1-2 weeks on the diet, but it dropped to low levels by 6 weeks. Lipoprotein preparations from plasmas of both C+- and C--fed animals inhibited NK cell activity, but suppression was not due to lipoprotein cholesterol content. On the basis of lipoprotein protein, lipoproteins from C--fed animals were more suppressive. The results suggest that the decrease in cytotoxicity induced by dietary cholesterol is due to more than the high levels of plasma and lipoprotein cholesterol.