NEDOCROMIL SODIUM SELECTIVELY INHIBITS IGE AND IGG4 PRODUCTION IN HUMAN B-CELLS STIMULATED WITH IL-4

We studied the effect of nedocromil sodium (NES) on human IgE and IgG subclass production. NES inhibited IgE and IgG4 production, without affecting IgM, IgA, IgG1, IgG2, or IgG3 production, by IL-4-stimulated mononuclear cells (MNC) obtained from non-atopic donors. Inhibition of IgE and IgG4 production by NES required the compound to be added on day 0 and to be present throughout the entire period of culture. Inhibition of IgE and IgG4 production was not mediated by known inhibiters, including IFN-alpha, IFN-gamma, transforming growth factor-beta, PGE2, or platelet-activating factor. Inhibition by NES required both T cells and monocytes because NES inhibited IgE production by B cells stimulated with IL-4 and anti-CD40 mAb in the presence, but not the absence, of T cells and monocytes. NES also inhibited IgE and IgG4 production in cultures stimulated with anti-CD3-treated T cells. However, in this case other isotypes were also inhibited by NES. In contrast to non-atopic donors' MNC, NES failed to inhibit spontaneous IgE and IgG4 production by MNC from atopic patients. However, NES was effective in inhibiting IL-4-induced IgE and IgG4 production in atopic patients' MNC without affecting IgM, IgA, IgG1, IgG2, or IgG3 production. NES inhibited IgE and IgG4 production by sIgE- and sIgG4- B cells, but not by sIgE+ and sIgG4+ B cells, respectively, stimulated with IL-4 or IL-4 plus anti-CD40 mAb in the presence of T cells and monocytes. These results suggest that NES may inhibit IL-4-induced switching of IgE and IgG4 production by sIgE- B cells and sIgG4- B cells, respectively, by affecting the interaction of B cells, T cells, and monocytes.