Neopterin Levels and Indoleamine 2,3-Dioxygenase Activity as Biomarkers of Immune System Activation and Childhood Allergic Diseases

Abstract

Background

Although Th2 immune activation is predominant in allergic diseases, neopterinlevels and indoleamine 2,3-dioxygenase (IDO)-1 activity (kynurenine:tryptophan ratio), which reflect Th1 immune activity, increase with interferon-gamma (IFN-γ) stimulation. We investigated neopterin, tryptophan, and kynurenine levels as biomarkersof the Th1 immune system activation and changes in IDO-1 activityin children with asthma, allergic rhinitis, and atopic dermatitis, as well as the relationship between these biomarkers and the total IgE level, age, and disease severity.

Methods

We divided 205 children (80 girls and 125 boys, four months to 17 years old) into four groups: controls, patients with asthma, patients with allergic rhinitis, and patients with atopic dermatitis. Peripheral venous blood samples were collected. Neopterin levels were determined by an enzyme immunoassay. Tryptophan and kynurenine levels were analyzed using HPLC. IDO-1 enzyme activity was calculated using tryptophan and kynurenine levels. IgE levels were measured. The Mann-Whitney U test, Kruskal-Wallis test, and Conover post-hoc method were used for statistical analysis.

Results

Neopterin, tryptophan, and kynurenine levels were higher and IgE levels and IDO-1 enzyme activity were lower in patients with asthma and allergic rhinitis than in controls ( P<0.05). Patients with atopic dermatitis showed higher neopterin, tryptophan, and kynurenine levels, higher IDO-1 activity, and lower IgE levels thancontrols ( P<0.05).

Conclusions

The Th1/Th2 balance is disrupted in children with allergic diseases, concomitant with increased Th1-mediated immune response activation and reduced IgEproduction, which is promoted by Th2-type cytokines.