Interferon administered in the cerebrospinal space and its effect on rabies in rabbits

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 (131)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.