Systemic Th1- and Th2-gene signals in atopy and asthma.
BACKGROUND
Atopic disorders have been associated with a Th-2 cytokine predominance. This study investigated Th1- and Th2-related gene expression in asthmatics, atopics and healthy individuals.


METHODS
We compared Th1- and Th2-related in vivo-signals using gene expression arrays in 18 atopic asthmatics, 8 atopic non-asthmatic and 14 healthy control subjects. Purified mRNA from peripheral blood mononuclear cells was reverse-transcribed and hybridised to cDNA membranes. Group differences were assessed after standardisation with Mann-Whitney U-test.


RESULTS
Atopic individuals had upregulated lymphotoxin-alpha and downregulated IFNGR1. On the other hand, they had particularly high IL-4, IL-5 and IL4R levels, together with significantly upregulated IL10. Asthmatic individuals had normal Th1-gene expression, but an upregulation og Th-2 genes. Atopic individuals had high, asthmatic individuals excessively high IL12RB1-levels. No Th-2 gene was downregulated in both atopic phenotypes. The expression of IL6R correlated with the daily dose of inhaled corticosteroids.


CONCLUSIONS
Atopic individuals had a down regulation of key TH1- and Th2-genes, resulting in a balanced upregulation of Th-specific genes. In contrast, asthmatic subjects had normal Th1-gene expression but a constant upregulation of Th2-specific genes, leading to Th2-predominance.
Joos
Ladina
L
Division of Respiratory Medicine and Pulmonary Cell Research, University Hospital Basel, Switzerland.
Carlen Brutsche
Ingrid E A
IE
Laule-Kilian
Kirsten
K
Crawen
Mark
M
Tamm
Michael
M
Brutsche
Martin H
MH
D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D018121:Receptors, Cytokine / Q000235:genetics*; D018417:Th1 Cells / Q000276:immunology / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics
D007378:Interleukins; D018121:Receptors, Cytokine; D016212:Transforming Growth Factor beta