Disturbed cytokine production at the systemic level in difficult-to-control atopic asthma: evidence for raised interleukin-4 and decreased interferon-γ release following lipopolysaccharide stimulation.
BACKGROUND
Disturbed cytokine production is thought to govern inflammation in asthma, which, in its turn, may lead to uncontrolled disease. The aim of this study was to assess the relationship between cytokine production from blood leucocytes and the level of asthma control.


METHODS
We compared the production of interleukin (IL)-4, IL-6, IL-10, interferon (IFN)-γ and tumour necrosis factor-α from peripheral blood leucocytes in non-atopic healthy subjects (n = 22), atopic non-asthmatics (n = 10), well-controlled asthmatics [Juniper asthma control questionnaire (ACQ) score <1.5; n = 20] and patients with uncontrolled asthma despite inhaled or oral corticoids (ACQ score ≥1.5; n = 20). Fifty microlitres of peripheral blood was incubated for 24 h with RPMIc, lipopolysaccharide (LPS; 1 ng/ml) or phytohaemagglutinin (1 μg/ml), and cytokines were measured by immunotrapping (ELISA).


RESULTS
Both controlled and uncontrolled asthmatics as well as atopic non-asthmatics spontaneously produced more IL-4 than non-atopic healthy subjects (p < 0.001). IL-4 production induced by LPS was significantly greater (p < 0.05) in both asthma groups compared to atopic non-asthmatics and non-atopic healthy subjects. By contrast, IFN-γ release induced by LPS was lower in uncontrolled asthmatics than in non-atopic healthy subjects (p < 0.05) and controlled asthmatics (p < 0.05). IL-10 release after LPS was greater in uncontrolled asthmatics than in atopic non-asthmatics (p < 0.05). No difference was observed regarding other cytokines.


CONCLUSIONS
Blood cells from patients with difficult-to-control atopic asthma display highly skewed Th2 cytokine release following LPS stimulation.
Department of Respiratory Medicine, CHU Sart-Tilman, GIGA Research Group i(3), Liège, Belgium. mmanise@student.ulg.ac.be
M
M
Manise
F
F
Schleich
V
V
Quaedvlieg
C
C
Moermans
M
M
Henket
J
J
Sele
J L
JL
Corhay
R
R
Louis
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D001249:Asthma / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins; D012720:Severity of Illness Index; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D016207:Cytokines; C508598:IL4 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma