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 (IFNalpha). SV infected control mice received i.p. saline. Antibodies against mouse IFNalpha 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 IFNalpha in the brain tissue. Also, mice that received IFNalpha neutralizing antibodies showed decreased presence of protein kinase R (PKR) measured by immunohistochemical densitometry, indicating the antibody successfully inhibited IFNalpha. The data shows that antibodies are capable of crossing the BBB and inhibiting IFNalpha, indicating that it is possible to target molecules of interest in the CNS with peripheral antibody treatment.
Sas
A
A
Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC, 29425, USA.
Jones
R
R
Tyor
W
W
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D016898:Interferon-alpha / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests
D000906:Antibodies; D016898:Interferon-alpha