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In Vivo Augmentation of Rat Lung Natural Killer Cell Activity and Inhibition of Experimental Metastases by Double-Stranded Polynucleotides¹

C.E.A.-I.P.S.N., Départment de Protection Sanitaire, Laboratoire de Toxicologie des Transuraniens, BP 12, 91680 Bruyères-Le-Chatel, France [D. N., E. A.], and INSERM U 245 and CNRS ER 238, Institut de Biologie Physico-Chimique, 13 Rue Pierre et Marie Curie, 75005 Paris, France [M. N. T.]

The in vivo effect on natural killer cell activity of the compound rl_n·r(C₁₂·U)_n, a mismatched nontoxic analogue of polyinosinicpolycytidylic acid [rl_n·rC_n], 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 rl_n·r(C₁₂·U)_n substantially enhanced natural killer cell activity to an extent comparable to the increase produced by rl_n·rC_n. 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.

¹ This work was supported by grants from the Centre National de la Recherche Scientifique (E.R. 238 et ATP "immunopharmacologie"), the Institut National de la Santé et de la Recherche Médicale, and the Fondation pour la Recherche Médicale.

² To whom requests for reprints should be addressed, at C. E. A., I. P. S. N., Départment de Protection Sanitaire, Laboratoire de Toxicologie des Transuraniens, BP 12, 91680 Bruyères le Chatel, France.

Received 3/12/84. Revised 6/13/85. Accepted 6/20/85.