Target-Organ Treatment of Neurotropic Virus Disease with Interferon Inducers

Abstract

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-μg amount of statolon, 30 μg 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.