SELECTIVE-INHIBITION OF SPONTANEOUS IGE AND IGG4 PRODUCTION BY INTERLEUKIN-8 IN ATOPIC PATIENTS

The effects of interleukin (IL)-8 on spontaneous IgE and IgG4 production in atopic patients were studied. IL-8 inhibited IgE and IgG4 production by purified surface (s) IgE(+) and sIgG4(+) B cells, respectively, while it had no effect on IgG1, IgG2, IgG3, IgM, IgA1, and IgA2 production by corresponding sIg(+) B cells. The IL-8-induced inhibition was counteracted by IL-6 and tumor necrosis factor-alpha (TNF-alpha) and was blocked by anti-IL-8 monoclonal antibody (MoAb). Conversely, the addition of anti-IL-6 MoAb and anti-TNF-alpha MoAb, in the absence of IL-8, inhibited IgE and IgG4 production by sIgE(+) and sIgG4(+) B cells, respectively. Purified sIgE(+) and sIgG4(+) B cells expressed IL-6 receptors (R), TNF-alpha R, and IL-8R, and they produced IL-6 and TNF-alpha, but not IL-8. IL-8 had no effect on IL-6R or TNF-alpha R, while it abrogated IL-6 and TNF-alpha production in these cells. In contrast, sIgG1(+), sIgG2(+), sIgG3(+), sIgM(+). sIgA1(+), and sIgA2(+) B cells expressed IL-6R and TNF-alpha R but not IL-8R, and they produced IL-6 and TNF-alpha. IL-8 had no effect on IL-6R and TNF-alpha R, or on TNF-alpha and IL-6 production in these cells. These results indicate that IL-8 inhibits spontaneous IgE and IgG4 production in sIgE(+) and sIgG4(+) B cells, respectively, by inhibiting the endogenous production of IL-6 and TNF-alpha. (C) 1995 by The American Society of Hematology.