Severely impaired IL-12/IL-18/IFNgamma axis in patients with hyper IgE syndrome.
BACKGROUND
Hyperimmunoglobulin E syndrome (HIES) is an inborn disorder characterized by recurrent skin and respiratory tract infections, skeletal abnormalities, chronic eczema and elevated serum IgE. The nature of the host defence defect has yet to be established. The aim of this study was to investigate whether activation of the interleukin-12/interleukin-18/interferon-gamma axis, known to be crucial for the activation of cellular immune responses, is impaired in patients with HIES.


METHODS
Cytokine production capacity of seven HIES patients and seven healthy controls was investigated in whole-blood cultures stimulated with heat-killed Staphylococcus aureus, Candida albicans, or a combination of interleukin (IL)-12/IL-18.


RESULTS
Interferon (IFN)gamma production, in addition to IFNgamma/IL-10 ratios, was 10-30-fold lower in the HIES patients compared with the healthy volunteers. In contrast TNF, IL-1beta and IL-8 production was normal.


CONCLUSIONS
These data revealed a severe dysbalance towards a Th2 phenotype in HIES patients which is likely to contribute to the specific pattern of infection susceptibility characteristic to HIES.
Netea
M G
MG
Radboud University Medical Centre and Nijmegen University Center for Infectious Diseases, Nijmegen, the Netherlands.
Kullberg
B J
BJ
van der Meer
J W M
JW
D000328:Adult; D016207:Cytokines / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology; D007589:Job Syndrome / Q000276:immunology*; D008297:Male; D018417:Th1 Cells / Q000276:immunology
D016207:Cytokines; D020382:Interleukin-18; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma