Mouse soluble IFN gamma receptor as IFN gamma inhibitor. Distribution, antigenicity, and activity after injection in mice.
With the purpose to use a soluble receptor as an IFN gamma antagonist in vivo, we assessed the immunogenicity, the half-life, the bioavailability, and the activity of the soluble receptor after injection into mice. No significant immunogenicity was detected after multiple chronic injections of mouse (Mo)IFN gamma-R or injections of MoIFN gamma-R in emulsion with CFA. Pharmacokinetic experiments using radiolabeled MoIFN gamma-R revealed that the half-life of the soluble MoIFN gamma-R is 3 h in the blood and 6 h in the lymphoid organs. When the MoIFN gamma-R protein was traced by the capacity of the animal sera to displace the binding of radiolabeled MoIFN gamma-R from affinity purified rabbit anti-MoIFN gamma-R antibodies, a blood half-life of 1 h was determined. Finally, the capacity of the injected receptor to bind and neutralize the IFN gamma-mediated antiviral activity was assessed in vivo. Treatment with IFN-gamma or IFN-alpha A/D protected the mice from the lethal infection with encephalomyocarditis virus. Mice treated with MoIFN-gamma-R neutralized the protective effect of IFN-gamma.
Ozmen
L
L
F. Hoffmann-La Roche Ltd, Pharmaceutical Research-New Technologies, Basel, Switzerland.
Gribaudo
G
G
Fountoulakis
M
M
Gentz
R
R
Landolfo
S
S
Garotta
G
G
D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017471:Receptors, Interferon / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D012995:Solubility; D014018:Tissue Distribution
D000941:Antigens; D017471:Receptors, Interferon; D007371:Interferon-gamma