SHIFTS IN INTERLEUKIN-4 AND INTERFERON-GAMMA PRODUCTION BY T-CELLS OF PATIENTS WITH ELEVATED SERUM IGE LEVELS AND THE MODULATORY EFFECTS OF THESE LYMPHOKINES ON SPONTANEOUS IGE SYNTHESIS

Interleukin-4 (IL-4) has been demonstrated to induce IgE synthesis by peripheral blood mononuclear cells (PBMNCs) of healthy donors. In this study, we demonstrated that IL-4 also can enhance spontaneous IgE synthesis by PBMNCs of allergic/atopic patients and patients with Buckley's or hyper-IgE syndrome. Spontaneous IgE production by PBMNCs of these patients was suppressed by interferon (IFN)-gamma or IFN-alpha in a dose-dependent fashion. Despite high serum IgE levels, no IL-4 could be detected in the serum of the patients, but indirect evidence was obtained indicating that enhanced IL-4 production in vivo may be associated with the high serum-IgE levels in these patients. Spontaneous IL-4 production was measured in PBMNC cultures of 4/21 patients tested. Furthermore, spontaneous IgE synthesis by PBMNCs of three other patients of seven tested in vitro was partly blocked by anti-IL-4 antiserum. In addition, levels of soluble CD23 (which is specifically induced by IL-4) were strongly elevated in sera of patients. Finally, activation of PBMNCs of the patients resulted in levels of IL-4 and of IFN-gamma synthesis that were higher and lower, respectively, than levels produced by PBMNCs of healthy control donors tested in parallel. Collectively, our data indicate that spontaneous IgE synthesis in vitro can be modulated by IL-4, IL-5, IFN-gamma, and IFN-alpha. In addition, our data suggest that enhanced IL-4 and reduced IFN-gamma production is associated with the elevated serum IgE levels observed in these patients.