In vivo augmentation of rat lung natural killer cell activity and inhibition of experimental metastases by double-stranded polynucleotides.

The in vivo effect on natural killer cell activity of the compound rln X r(C12 X U)m, a mismatched nontoxic analogue of polyinosinic-polycytidylic acid [rln X rCn], was tested in inbred Wistar AG rats by measuring the natural killer cell activity of lymphocytes freshly isolated from lung capillaries. Lysis was measured in a 4-h chromium release assay using YAC-1 or syngeneic P77 lung tumor cells as target. Treatment of an animal with rln X r(C12 X U)n substantially enhanced natural killer cell activity to an extent comparable to the increase produced by rln X rCn. This boosting of natural killer activity was correlated closely with a decrease in the incidence of experimental pulmonary metastasis. However, the beneficial effect lasted for only a short period after stimulation, due to the transient nature of double stranded polynucleotide enhancement and to the concomitantly rapid extravasation of tumor cells into the lung parenchyma. It is concluded that natural killer cells are important in host defense against circulating tumor cells and can be boosted by nontoxic mismatched double stranded polynucleotides.