Inhibition of human IgE synthesis in vitro and in SCID-hu mice by an interleukin-4 receptor antagonist.
In the present study, it is shown that a human interleukin (IL)-4 mutant protein (IL-4.Y124D) acts as a potent IL-4 and IL-13 receptor antagonist. Human (h) IL-4.Y124D efficiently inhibits both IL-4- and IL-13-induced IgE production in vitro. In addition, hIL-4.Y124D strongly inhibits ongoing human IgE synthesis in SCID-hu mice. These inhibitory effects are specific, since human IgG levels were not significantly affected. These results confirm the notion that the IL-4 and IL-13 receptor share a common component, which is required for signal transduction. In addition, they show that relatively large antagonistic polypeptides, such as hIL-4.Y124D have potential clinical utility in reducing IgE-mediated allergic diseases.
Carballido
J M
JM
Human Immunology Department, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304-1104, USA.
Aversa
G
G
Schols
D
D
Punnonen
J
J
de Vries
J E
JE
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001667:Binding, Competitive; D016025:Bone Transplantation; D002678:Chimera; D016332:Fetal Tissue Transplantation; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000031:analogs & derivatives* / Q000235:genetics / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D016513:Mice, SCID; D016297:Mutagenesis, Site-Directed; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors*; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D015398:Signal Transduction / Q000187:drug effects; D013950:Thymus Gland / Q000196:embryology / Q000637:transplantation; D014183:Transplantation, Heterologous; D016042:Transplantation, Heterotopic
C508181:IL13RA1 protein, human; C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D007073:Immunoglobulin E