NEDOCROMIL SODIUM ACTS DIRECTLY ON HUMAN B-CELLS TO INHIBIT IMMUNOGLOBULIN PRODUCTION WITHOUT AFFECTING CELL-GROWTH

The effect of nedocromil sodium (NES) on human immunoglobulin (Ig) iso types, IgG subclasses and IgA subclasses was studied. NES inhibited Ig M and IgA1 production from human lymphoblastoid B-cell lines CBL and G M-1056, respectively, in a dose-dependent fashion. This inhibition was not due to decreased cell growth as cell proliferation was not affect ed by NES and cell viability was always greater than 98%. Of the vario us cytokines tested, interleukin-4 (IL-4) reduced the NES-induced inhi bition of Ig production, whereas other cytokines, including IL-1 beta, IL-2, IL-3, IL-5, IL-6, interferon-alpha (IFN-alpha), IFN-gamma, gran ulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoiet in (Epo) failed to do so. The reducing effect of IL-4 was blocked by a nti-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 r educed by IL-4 specifically. These results indicate that in addition t o its anti-allergic function, NES may act as a B-cell regulatory reage nt.