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Modified polyriboinosinic-polyribocytidylic acid complex: sustained interferonemia and its physiological associates
Abstract:
Fourteen patients with severe viral illnesses were given intravenous infusions of a modified interferon inducer, polyriboinosinic-polyribocytidylic acid-poly-L-lysine complexed with carboxymethylcellulose [poly)I:C.LC)], during a phase 1 clinical trial. The first eight patients received 0.15 to 0.30 mg of poly(I:C.LC) per kg of body weight daily for 5 consecutive days, and another received two courses separated by 1 week. A second group of five patients was given single intravenous infusions of 0.10 to 0.15 mg of poly(I:C.LC) per kg. Interferon was detectable in the serum 8 to 16 h after injection. Titers ranged from 15 to 800 U/ml and varied directly with the dose of poly(I:C.LC). Interferonemias persisted for 12 to 48 h. In patients receiving 5-day courses of poly(I:C.LC), lower levels of serum interferon (0 to 160 U/ml) occurred on days 2 through 5, characteristic of a hyporesponsive state. An exception was a 69-year-old patient with disseminated varicella zoster, multiple myeloma, and renal insufficiency whose serum contained 3,150 U of interferon per ml on day 3 of 0.3 mg of poly(I:C.LC) per kg. Fever (39 to 40.5 degrees C, rectally; 13 of the 14 patients) peaked 3 to 8 h after completion of infusions. Other toxic effects included lymphopenia (10 of the 14 patients), hypotensive episodes (7 of the 14 patients), and minor elevations of serum glutamicoxalacetic transaminase and lactic dehydrogenase.
Insights
This phase 1 trial investigated polyriboinosinic-polyribocytidylic acid-poly-L-lysine complexed with carboxymethylcellulose [poly(I:C.LC)] as an interferon inducer in severe viral illnesses. The study found dose-dependent interferon production, with notable fever and lymphopenia as side effects.
Area of Science:
- Immunology
- Virology
- Pharmacology
Background:
- Severe viral illnesses pose significant therapeutic challenges.
- Interferon inducers represent a potential treatment strategy.
- Poly(I:C.LC) is a modified interferon inducer investigated for clinical use.
Purpose of the Study:
- To evaluate the safety and interferon-inducing capacity of poly(I:C.LC) in patients with severe viral illnesses.
- To determine the dose-response relationship of poly(I:C.LC) and serum interferon levels.
- To identify potential toxicities associated with poly(I:C.LC) administration.
Main Methods:
- Phase 1 clinical trial involving 14 patients with severe viral illnesses.
- Intravenous administration of poly(I:C.LC) at varying doses and schedules.
- Monitoring of serum interferon levels, duration of interferonemia, and adverse events.
Main Results:
- Interferon was detected in serum 8-16 hours post-injection, with titers directly correlating to poly(I:C.LC) dose (15-800 U/ml).
- Interferon levels persisted for 12-48 hours; however, a hyporesponsive state was observed during 5-day treatment courses.
- Common adverse effects included fever (13/14 patients), lymphopenia (10/14), and hypotensive episodes (7/14).
Conclusions:
- Poly(I:C.LC) effectively induces serum interferon in patients with severe viral illnesses.
- Dose and administration schedule influence interferon production and potential hyporesponsiveness.
- Fever and lymphopenia are notable toxicities requiring consideration in clinical application.