Free and liposome-encapsulated double-stranded RNAs as inducers of interferon, interleukin-6, and cellular toxicity.
Poly(rI:rC) and Ampligen were entrapped in liposomes that were covalently coupled to Protein A, permitting binding to antibodies specific for the major histocompatibility complex-encoded H2K molecule of L929 cells, or to control antibodies. Free and encapsulated polynucleotides were compared for their capacity to stimulate secretion of interferon (IFN) and interleukin-6 (IL-6) and to induce cellular toxicity on L929 cells pretreated with IFN-alpha/beta. Free and encapsulated poly(rI:rC) or Ampligen (poly(rI:rC12-rU] induced similar levels of secretion of IFN over a broad dose range. The activity of the liposome-encapsulated polynucleotides was dependent on its binding to an antibody that permitted cell association and internalization; the same liposomes were inactive in the presence of control antibodies. IL-6 secretion was induced by double-stranded (ds) RNA in a dose-dependent manner, with a significantly greater effect seen for targeted, liposome-encapsulated material. The marked toxicity of targeted poly(rI:rC), as compared to free poly(rI:rC), was confirmed. Encapsulated Ampligen was less toxic than encapsulated Poly(rI:rC).
Milhaud
P G
PG
Laboratoire de Biochimie des Protéines URA CNRS 1191, Université de Montpellier II, France.
Machy
P
P
Colote
S
S
Lebleu
B
B
Leserman
L
L
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D007369:Interferon Inducers / Q000008:administration & dosage* / Q000633:toxicity; D015850:Interleukin-6 / Q000096:biosynthesis*; D008081:Liposomes; D012330:RNA, Double-Stranded / Q000008:administration & dosage* / Q000633:toxicity
D004337:Drug Carriers; D007369:Interferon Inducers; D015850:Interleukin-6; D008081:Liposomes; D012330:RNA, Double-Stranded