Immunomodulation with soluble IFN-gamma receptor: preliminary study.
Several in vivo experiments support the hypothesis that an IFN-gamma antagonist may have therapeutic applications in autoimmune diseases, hypersensitivities, and alloreactions. IFN-gamma exerts its biological activity through the binding to a single-chain cell surface receptor. The protein that corresponds to the external domain of mouse IFN-gamma receptor was expressed in insect cells infected with recombinant baculovirus; this protein was characterized and used in vivo as a prototype of the IFN-gamma antagonist. This protein does not show any strong antigenicity after in vivo injection in mice. Despite a blood half-life of only 1-3 hr as demonstrated in pharmacokinetic experiments, the mouse soluble IFN-gamma R was able to modify the onset of acute GVHD (alloreaction) and chronic GVHD (lupuslike disease).
Ozmen
L
L
Hoffmann-La Roche Ltd., CH-4002 Basel, Switzerland.
Fountoulakis
M
M
Gentz
R
R
Garotta
G
G
D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D002908:Chronic Disease; D006086:Graft vs Host Disease / Q000628:therapy; D007371:Interferon-gamma; D051379:Mice; D008810:Mice, Inbred C57BL / Q000276:immunology; D008811:Mice, Inbred DBA / Q000276:immunology; D008969:Molecular Sequence Data; D010599:Pharmacokinetics; D017471:Receptors, Interferon / Q000276:immunology; D012995:Solubility; D000096743:Interferon gamma Receptor
D000276:Adjuvants, Immunologic; D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor