title: Immunomodulation of natural killer activity by polyribonucleotides.
abstract: 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.
mesh_terms: D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000494:pharmacology / Q000031:analogs & derivatives; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D007369:Interferon Inducers / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008099:Liver / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011063:Poly A-U / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D011107:Polylysine / Q000494:pharmacology / Q000031:analogs & derivatives; D011131:Polyribonucleotides / Q000494:pharmacology*; D013154:Spleen / Q000276:immunology; D013329:Structure-Activity Relationship
chemical_list: D007369:Interferon Inducers; D011131:Polyribonucleotides; D011063:Poly A-U; D011107:Polylysine; C019531:poly ICLC; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C