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Background: The hyper-IgE syndrome is a primary immunodeficiency characterized by severe recurrent abscesses, pneumonia with pneumatocele formation, and elevated serum IgE. Eosinophilia, neutrophil chemotactic defects, and marked tissue damage are frequently present in this syndrome., Objective: To study whether functional changes in cytokines, adhesion molecules, and neutrophils might help explain these clinical observations., Methods: The following functions were analyzed in patients with the hyper-IgE syndrome and in controls: (1) production of granulocyte-macrophage-colony-stimulating factor by peripheral blood mononuclear cells by ELISA; (2) respiratory burst and reactive oxygen intermediates production by peripheral neutrophils using the luminol-enhanced chemiluminescense technique; and (3) expression of L-selectin on granulocytes and lymphocytes by flow cytometry., Results: Patients with hyper-IgE syndrome had significantly increased production of granulocyte-macrophage-colony-stimulating factor by resting or stimulated mononuclear cells, increased generation of reactive oxygen intermediates by neutrophils treated with opsonized zymosan, and reduced L-selectin expression on quiescent and activated granulocytes and lymphocytes., Conclusions: Our results suggest that an important feature of the hyper-IgE syndrome is the increased production of granulocyte-macrophage-colony-stimulating factor, which may explain the reduced L-selectin expression, decreased chemotaxis, and increased oxygen radical production and tissue damage in this disease.

Background: Enhanced production of TH-2 cytokines plays a key role in increased IgE production in allergic diseases. Reports about the cytokine profile secreted by peripheral blood mononuclear cells of patients with hyper-IgE syndrome, however, are controversial, suggesting alternative causes for increased IgE production in this syndrome., Objective: We wished to determine whether mononuclear cells from patients with hyper-IgE syndrome have a pattern of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) production characteristic of a predominance of TH-2 cells and whether the cytokine production pattern is constant over time., Methods: IL-4 and IFN-gamma secretion by peripheral blood mononuclear cells stimulated with phytohemagglutinin and D. pteronyssinus was measured by ELISA in culture supernatants. Patients with the hyper-IgE syndrome were evaluated 3 times at 4-week intervals and compared with asthmatic patients and normal subjects., Results: In PHA-stimulated cultures, patients with hyper-IgE syndrome had an IL-4 and IFN-gamma secretion similar to that of controls, while asthmatic patients had increased IL-4 and decreased IFN-gamma production. Cultures stimulated with D. pteronyssinus showed a variable pattern of secretion for both cytokines., Conclusions: In allergic diseases, increased serum IgE level is the result of a TH-2 pattern of cytokine production, with high IL-4 and decreased IFN-gamma protein secretion. The increased serum IgE concentration typical of the hyper-IgE syndrome is likely the result of a different immunoregulatory process.