title: Modulation of cell-bound and soluble CD23, spontaneous and ongoing IgE synthesis of human peripheral blood mononuclear cells by soluble IL-4 receptors and the partial antagonistic IL-4 mutant protein IL-4 (Y124D).
abstract: We studied the influence of human recombinant soluble interleukin-4 receptors (sIL-4R) and a partial antagonistic mutant IL-4 protein, IL-4(Y124D), on the in vitro CD23 expression, soluble (s)CD23 release and IgE synthesis of human peripheral blood mononuclear cells (PBMC). The data show that sIL-4R suppressed the IL-4-induced IgE synthesis of PBMC. sIL-4R fusion protein stabilized with human Fc gamma fragments showed a more pronounced effect than unconjugated sIL-4R. IL-4(Y124D) also suppressed the IL-4-induced IgE synthesis. The IL-4-induced antigen CD23 and its soluble fragments were suppressed by sIL-4R and IL-4(Y124D). PBMC of atopic donors with a spontaneous in vitro IgE synthesis showed a partial suppression of the IgE production after sIL-4R or IL-4(Y124D) application. The IgE synthesis and sCD23 release of normal donor PBMC were suppressed when the substances were applied 0-4 days after IL-4 treatment. After 4 days of IL-4 stimulation, sIL-4R and IL-4(Y124D) enhanced the IgE synthesis. These data demonstrate that sIL-4R and IL-4(Y124D) are suppressive for the primary IgE synthesis induced by IL-4. In contrast, the ongoing IgE synthesis was only partially modulated by sIL-4R and IL-4(Y124D), and in some conditions even an enhancement of the IgE production was observed. These data suggest a differential function for IL-4 in the early and late phase of PBMC IgE production.
authors.affiliation: Medizinische Mikrobiologie und Immunologie, AG Infektabwehrmechanismen, Ruhr-Universität Bochum, Germany.
authors.forename: B
authors.initials: B
authors.lastname: König
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: W
authors.initials: W
authors.lastname: König
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000276:immunology*; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000276:immunology*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D017455:Receptors, IgE / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000276:immunology*; D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins / Q000276:immunology; D012995:Solubility
chemical_list: D015703:Antigens, CD; D017455:Receptors, IgE; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E