Interferon Induction in Cynomolgus and Rhesus Monkeys After Repeated Doses of a Modified Polyriboinosinic-Polyribocytidylic Acid Complex

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Abstract
Serum interferon activity was determined in 12 cynomolgus and 12 rhesus monkeys injected intravenously once daily for 10 days with from 0.1 to 6.0 mg of a stabilized polyriboinosinic acid · polyribocytidylic acid complex per kg, composed of polyriboinosinic acid · polyribocytidylic acid, poly-1-lysine, and carboxymethylcellulose [poly(ICLC)]. Interferon activity was detected 2 h after the first injection, with maximum activity occurring 8 h after the second injection. A period of hyporesponsiveness occurred after the third injection of poly(ICLC) in all monkeys and lasted until the sixth injection in the rhesus monkeys, when interferon activity again became more elevated. The delayed rebound was not as apparent in cynomolgus monkeys. Rhesus monkeys injected with 6 mg/kg did not exhibit serious side effects.