Target-organ treatment of neurotropic virus disease with interferon inducers.
Interferon inducers were used against vaccinial encephalitis to study the target-organ treatment of neurotropic disease and to correlate interferon levels and the antiviral state following such treatment. A 45-mug amount of statolon, 30 mug of polyribinosinic-polyribocytidylic acid complex (poly I.poly C), or 0.0154 HA unit of Sendai virus given intracerebrally protected 100% of mice challenged the next day with 1,000 median lethal doses (LD(50)) of vaccinia virus. Significant protection against 1,000 LD(50) of vaccinia virus persisted for 1, 4, or 3 weeks after poly I.poly C, statolon, or Sendai virus (154 HA units), respectively. These doses of poly I.poly C and statolon were also used to study postinfection treatment. Mice challenged with 1, 10, 100, or 1,000 LD(50) were treated intracerebrally with poly I.poly C or statolon 24 or 48 hr later. Significant increases in survival time were seen in mice challenged with 1 to 100 LD(50) of vaccinia virus and treated 24 hr later. At challenges of 10 or 100 LD(50), statolon was more effective than poly I.poly C in increasing survival times. When treatment was delayed until 48 hr after infection, significant increases in survival time occurred only when the challenges were in the range of 1 to 10 LD(50), with poly I.poly C and statolon being equally effective. Interferon was measured by Finter's dye-uptake method, with L-929 cells and Semliki Forest virus. Poly I.poly C, statolon, or Sendai virus, given intracerebrally to mice, produced serum interferon peaks of 5,120 units/ml at 2 hr, 2,560 units/ml at 12 hr, or 320 units/ml at 18 hr, respectively. Corresponding brain interferon peaks were 640 units/g at 2 hr, 640 units/g at 4 to 24 hr, and 960 units/g at 72 hr.
D000818:Animals; D001923:Brain Chemistry; D004395:Dye Dilution Technique; D004673:Encephalomyelitis, Acute Disseminated / Q000188:drug therapy* / Q000276:immunology; D007369:Interferon Inducers / Q000627:therapeutic use*; D007372:Interferons / Q000032:analysis / Q000097:blood; D051379:Mice; D010222:Parainfluenza Virus 1, Human / Q000276:immunology; D011070:Poly I-C; D011134:Polysaccharides / Q000627:therapeutic use; D012672:Semliki forest virus / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology
D007369:Interferon Inducers; D011134:Polysaccharides; D007372:Interferons; D011070:Poly I-C