REDUCED INTERFERON-GAMMA BUT NORMAL IL-4 AND IL-5 RELEASE BY PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM XHOSA CHILDREN WITH ATOPIC ASTHMA

Background: Allergic asthma is increasing in black South Africans, a c ohort with inherently high basal IgE levels. Atopy has been linked to an excess of the T helper 2 cytokines IL-4 and IL-5 relative to the T helper 1 cytokine interferon-gamma (IFN-gamma); however, most studies have utilized T cell clones. Studies on peripheral blood mononuclear c ells (PBMC) have shown decreased IFN-gamma release in patients with at opic dermatitis. It is uncertain whether this finding extends to atopi c asthma. Objectives: To characterize cytokine release by mitogen-acti vated PBMC from Xhosa children and to investigate whether reduced IFN- gamma release is a feature of atopic asthma and whether there is a rel ationship between cytokine profiles and asthma severity. Methods: Cyto kine release and proliferation of phytohemagglutinin-stimulated PBMC f rom 10 patients with severe asthma and 14 patients with moderate asthm a (highly allergic to house dust mites) and 17 healthy controls was as sessed. Total serum, allergen-specific, and Ascaris-specific IgE was m easured. Results: Proliferation did not differ between the groups. The release of IFN-gamma was progressively decreased (and the IL-4/ IFN-g amma ratio increased) in the groups with moderate or severe asthma. Tu mor necrosis factor-alpha release was reduced, but IL-4, IL-5, and gra nulocyte-macrophage-colony stimulating factor release was unchanged. T he presence of Ascaris-specific IgE did not influence the cytokine pro files. Conclusion: Our study extends the findings observed for other a topic disorders and suggests that defective IFN-gamma release is a gen eralized feature of atopic diseases. This study- the first to investig ate both severe and moderate asthma, with the groups having similar at opic profiles-indicates that the extent of the defect in IFN-gamma rel ease might be related to asthma severity.