Indoleamine 2,3-dioxygenase (IDO) activity is lower in atopic than in non-atopic individuals and is enhanced by environmental factors protecting from atopy.
Tryptophan catabolism activated by the indoleamine 2,3-dioxygenase (EC 1.13.11.42) (IDO) enzyme in antigen presenting cells has a central role in induction of mechanisms suppressing T cell activation or clonal expansion. There is evidence suggesting that IDO activity is mainly upregulated by typical Th1-differentiating signals such as interferon-gamma and bacterial lipopolysaccharide (LPS). Therefore, we hypothesized that IDO activity would be lower in a Th2-associated disease such as atopy and that it would be higher in the presence of environmental factors known to favor Th1 differentiation. Here we show that this was the case. Concentrations of tryptophan (trp) and kynurenine (kyn), the main metabolite, were determined by reverse phase liquid chromatography from serum samples of a cohort of 392 non-asthmatic individual of whom 149 were atopics (one or more positive skin test when tested with a panel of 22 allergens). Kyn/trp ratio, as an indicator of IDO activity, was significantly lower in atopic than in non-atopic individuals. The cohort was stratified according to two known atopy-protecting factors, presence of antibodies against Helicobacter pylori or anamnestic information about childhood on a farm environment. As expected, IDO activity was significantly higher in their presence than absence.
University of Tampere Medical School, Tampere, Finland. annika.raitala@uta.fi
Annika
A
Raitala
Jussi
J
Karjalainen
Simo S
SS
Oja
Timo U
TU
Kosunen
Mikko
M
Hurme
D000907:Antibodies, Bacterial / Q000097:blood; D015331:Cohort Studies; D015536:Down-Regulation; D004777:Environment; D005260:Female; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000201:enzymology* / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007737:Kynurenine / Q000097:blood; D008297:Male; D018418:Th2 Cells / Q000276:immunology*; D014364:Tryptophan / Q000097:blood
D000907:Antibodies, Bacterial; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan