Interferon Administered in the Cerebrospinal Space and Its Effect on Rabies in Rabbits

Abstract

Because combined administration of intramuscular and intravenous interferon has been partially successful in the incubationary treatment of rabies, the effect of direct interferon administration into the cerebrospinal fluid space was tested. After injecting 1,800 U of interferon into the cisterna magna or the lateral ventricle, periodic samples, obtained by cisternal taps, showed that 1 to 5% remained after 24 h, as opposed to the known clearance of interferon from the bloodstream to this level within minutes. The distributions of interferon and 13"I-labeled albumin were similar as demonstrated by kinetics of clearance monitored over 24 h. Beginning with and after experimental infection of rabbits, daily intraventricular injections of one million units of interferon were given for as long as 3 weeks. Interferon was prepared from cell culture fluids after pressure dialysis and chromatography on Sephadex G-100. This intensive treatment did not prevent encephalitis, but prolonged the length of the incubation period by one-to two-thirds. The outcome after intraventricular administration was not as favorable as when one million units equally divided between intramuscular and intravenous injections were given at the time of challenge. Interferon administered in the subarachnoid space in this fashion is apparently inadequate to protect the rabbit against rabies. Its role as an adjunct measure, or other methods of administration in the nervous system, remains to be examined.

Use of Interferon in the Management of Patients With Subacute Sclerosing Panencephalitis

“…Subsequent samples of CSF showed the presence of interferon, indicating that following an intrathecal injection it remained present in CSF for at least 24 hours. This finding has been noted in animal work (Ho et al 1974, Habif et af. 1975, Hilfenhaus ef al.…”

Antiviral activities of interferons

“…inject interferon either intramuscularly or intravenously, and then analyze for interferon in cerebrospinal fluid. The animals tested include mice, hamsters, rabbits, monkeys and humans; the sites of injections include cerebrum, theca vertebralis, cisterna magna, lateral ventricle, directly into the cerebrospinal fluid, and lumbar-spinal; inducers include poly(rI).poly(rC), blue tongue virus, rabies virus, and Sendai virus (Kono and Ho, 1965;Ho and Ke, 1970;Cathala and Baron, 1970;Jameson et al, 1977;Stewart II and Sulkin, 1966;Allen and Cochran, 1972;Ho et al, 1974;Habif et al, 1975;Hilfenhaus et al, 1977b). The overwhelming agreement among all the studies reported was encouraging.…”