Endogenous interleukin 6 plays an obligatory role in interleukin 4‐dependent human IgE synthesis

The lymphokine interleukin (IL) 4 plays a crucial role in the regulation of IgE synthesis. In the present study, the cellular and cytokine requirements for the IL 4‐dependent induction of IgE synthesis in humans were analyzed. Recombinant IL4 could induce IgE synthesis by peripheral blood mononuclear cells and autologous T/B cell mixtures, but not by highly purified B cells. IgE induction by IL4 was strongly decreased in monocyte‐depleted peripheral blood mononuclear cells. These results show that the induction of IgE synthesis by recombinant IL 4 is T cell dependent and optimal in the presence of monocytes. IL5 and IL6, but not IL2, IL1 and tumor necrosis factor‐α, strongly up‐regulated the IL4‐dependent synthesis of IgE, with modest effects on cell proliferation. An anti‐IL6 polyclonal antibody strongly inhibited IL4‐driven IgE production. Endogenous IL6 plays, therefore, an obligatory role in the IL4‐dependent induction of IgE. However, a combination of IL 4, IL 5 and IL 6 (with or without IL 1) at optimal concentrations could not induce IgE synthesis by purified normal B cells, indicating that cytokine‐mediated signals, although essential, are not sufficient for the IL 4‐dependent induction of IgE synthesis.