The cooperative effect of interferon-alpha and ribavirin on subacute sclerosing panencephalitis (SSPE) virus infections, in vitro and in vivo.
We studied the effects of two antiviral agents, human interferon-alpha (IFN-alpha) and ribavirin, on subacute sclerosing panencephalitis (SSPE) virus infections in hamsters. By intracranial administration, IFN-alpha alone improved the survival of infected hamsters by 20% at a dose of 6 x 10(4) IU/kg every other day for 10 days. When the dose of IFN-alpha was increased incrementally to 6 x 10(6) IU/kg, the survival rate increased by 70% in a dose-dependent manner. The combination of IFN-alpha and ribavirin had a synergic inhibitory effect on the replication of SSPE virus in cell culture. Combination of IFN-alpha (at a dose of 6 x 10(5) IU/kg) with ribavirin (at a dose of 1 mg/kg) completely prevented mortality. This was significantly better than either IFN-alpha or ribavirin monotherapy (p < 0.05). Under the conditions used, IFN-alpha did not enhance the toxicity of ribavirin in hamsters. Intraventricular administration of high dose IFN-alpha and ribavirin may have potential usefulness in the treatment of patients with SSPE.
Takahashi
T
T
Department of Microbiology, Fukushima Medical College, Hikarigaoka, Japan.
Hosoya
M
M
Kimura
K
K
Ohno
K
K
Mori
S
S
Takahashi
K
K
Shigeta
S
S
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D001921:Brain / Q000821:virology; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D008647:Mesocricetus; D012254:Ribavirin / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D013190:SSPE Virus / Q000187:drug effects* / Q000502:physiology; D013344:Subacute Sclerosing Panencephalitis / Q000188:drug therapy* / Q000821:virology; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin