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 cohort 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 cells (PBMC) have shown decreased IFN-gamma release in patients with atopic dermatitis. It is uncertain whether this finding extends to atopic asthma.


OBJECTIVE
To characterize cytokine release by mitogen-activated PBMC from Xhosa children and to investigate whether reduced IFN-gamma release is a feature of atopic asthma and whether there is a relationship between cytokine profiles and asthma severity.


METHODS
Cytokine release and proliferation of phytohemagglutinin-stimulated PBMC from 10 patients with severe asthma and 14 patients with moderate asthma (highly allergic to house dust mites) and 17 healthy controls was assessed. Total serum, allergen-specific, and Ascaris-specific IgE was measured.


RESULTS
Proliferation did not differ between the groups. The release of IFN-gamma was progressively decreased (and the IL-4/IFN-gamma ratio increased) in the groups with moderate or severe asthma. Tumor necrosis factor-alpha release was reduced, but IL-4, IL-5, and granulocyte-macrophage-colony stimulating factor release was unchanged. The presence of Ascaris-specific IgE did not influence the cytokine profiles.


CONCLUSIONS
Our study extends the findings observed for other atopic disorders and suggests that defective IFN-gamma release is a generalized feature of atopic diseases. This study-the first to investigate both severe and moderate asthma, with the groups having similar atopic profiles-indicates that the extent of the defect in IFN-gamma release might be related to asthma severity.
Nurse
B
B
Department of Immunology, University of Cape Town, South Africa.
Haus
M
M
Puterman
A S
AS
Weinberg
E G
EG
Potter
P C
PC
D000293:Adolescent; D001249:Asthma / Q000097:blood* / Q000453:epidemiology / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood / Q000453:epidemiology; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D015848:Interleukin-5 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D013019:South Africa / Q000453:epidemiology
D016207:Cytokines; D015848:Interleukin-5; D010835:Phytohemagglutinins; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma