Immunomodulation of natural killer activity by polyribonucleotides

Several synthetic polyribonucleotides have been examined for the ability to augment natural killer (NK) activity and induce interferon (IFN) production. The results demonstrate that the complex of polyinosinic-polycytidylic acid and poly-L-lysine, which has been stabilized in carboxymethylcellulose [poly(I,C)-LC], polyadenylic-polyuridylic acid [poly(A).poly(U)], and a labile poly (I,C) compound with mismatched bases, designated poly(I).poly(C12U), all augment NK activity. However, poly(A).poly(U) and poly(I).poly(C12U) are less efficient augmentors of NK activity on a milligram per kilogram basis, than is poly(I,C)-LC. Similarly, poly(I,C)-LC induces more serum IFN following administration of 1, 10, or 100 micrograms/mouse (1,000-10,000 U/ml) than does either poly(A).poly(U) (0-25 U/ml) or poly(I).poly(C12U) (0-250 U/ml) at the same doses. Further studies with poly(I,C)-LC demonstrated that this molecule is an excellent augmentor of liver-associated NK activity. In fact, administration of poly(I,C)-LC resulted in higher NK levels in lever (63% lysis) than in spleen (44%) or blood (36%), and the augmented NK response was maintained in the liver for up to 13 days, whereas levels of NK activity in both blood and spleen returned to normal by days 3-6.