title: Nedocromil sodium acts directly on human B cells to inhibit immunoglobulin production without affecting cell growth.
abstract: The effect of nedocromil sodium (NES) on human immunoglobulin (Ig) isotypes, IgG subclasses and IgA subclasses was studied. NES inhibited IgM and IgA1 production from human lymphoblastoid B-cell lines CBL and GM-1056, respectively, in a dose-dependent fashion. This inhibition was not due to decreased cell growth as cell proliferation was not affected by NES and cell viability was always greater than 98%. Of the various cytokines tested, interleukin-4 (IL-4) reduced the NES-induced inhibition of Ig production, whereas other cytokines, including IL-1 beta, IL-2, IL-3, IL-5, IL-6, interferon-alpha (IFN-alpha), IFN-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo) failed to do so. The reducing effect of IL-4 was blocked by anti-IL-4 antibody but not by control IgG. Moreover, IFN-alpha and IFN-gamma, but not GM-CSF, overcame the reducing effect of IL-4. NES also inhibited production of IgM, IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2 by tonsillar B cells stimulated with Staphylococcus aureus Cowan strain I (SAC) and IL-6 without affecting proliferation. This inhibition was reduced by IL-4 specifically. These results indicate that in addition to its anti-allergic function, NES may act as a B-cell regulatory reagent.
authors.affiliation: Department of Pediatrics, Kyoto University Hospital, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kimata
authors.forename: M
authors.initials: M
authors.lastname: Fujimoto
authors.forename: H
authors.initials: H
authors.lastname: Mikawa
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D007700:Kinetics; D017835:Nedocromil / Q000494:pharmacology*; D014066:Palatine Tonsil / Q000276:immunology
chemical_list: D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D017835:Nedocromil