Modified polyriboinosinic-polyribocytidylic acid complex: induction of serum interferon, fever, and hypotension in rabbits

Abstract

The purposes of this study were to determine whether the febrile and hypotensive reactions to the administration of polyriboinosinic-polyribocytidylic acid [poly (I)-poly (C)] complexed with poly-L-lysine and carboxymethylcellulose (poly ICLC) (9S) encountered in humans could be duplicated in rabbits, and when such duplication was demonstrated, to ascertain whether these untoward reactions could be avoided by (i) administration of hydrocortisone (HC), (ii) alteration of the route of delivery, or (iii) administration of poly ICLC (4S) an interferon inducer of lower molecular weight. Responses to intravenous poly ICLC (9S) in rabbits reproduced adverse reactions in humans, namely fever and hypotension, and were accompanied by high titers of serum interferon. Continuing investigations showed that (i) intravenous pretreatment of rabbits with HC ameliorated hypotensive responses but markedly diminished interferon induction. When HC was given after poly ICLC (9S), both interferon and hypotension induction were likewise depressed. (ii) Intramuscular or subcutaneous poly ICLC (9S) produced neither high titers of serum interferon nor toxic effects. (iii) Poly ICLC (4S) induced high titers of serum interferon and fever, but no hypotension. Poly ICLC (4S) warrants further study.