Intra-peritoneal injection of polyclonal anti-interferon alpha antibodies cross the blood brain barrier and neutralize interferon alpha

The central nervous system (CNS) is known to be an immunologically privileged organ in the body largely because the blood brain barrier (BBB) prevents the flow of large molecules, proteins, and cells from crossing into the CNS from the periphery. These restrictive properties of the BBB have made it difficult to treat CNS diseases. In this study, mice were infected intracranially (i.c.) with Sindbis virus (SV) and then treated either i.c. or intraperitoneally (i.p.) with neutralizing antibodies against interferon alpha (IFN alpha). SV infected control mice received i.p. saline. Antibodies against mouse IFN alpha were detected in the brain tissue of mice that received i.p. and i.c. injections of the antibody. ELISA analysis showed that both i.c. and i.p. antibody treated mice had significantly decreased levels of IFN alpha in the brain tissue. Also, mice that received IFN alpha neutralizing antibodies showed decreased presence of protein kinase R (PKR) measured by immunohistochemical densitometry, indicating the antibody successfully inhibited IFN alpha. The data shows that antibodies are capable of crossing the BBB and inhibiting IFN alpha, indicating that it is possible to target molecules of interest in the CNS with peripheral antibody treatment.