Cytokine profiles in asthma families depend on age and phenotype

Abstract

Background: Circulating cytokine patterns may be relevant for the diagnosis of asthma, for the discrimination of certain phenotypes, and prognostic factors for exacerbation of disease.

Methodology/principal findings: In this study we investigated serum samples from 944 individuals of 218 asthma-affected families by a multiplex, microsphere based system detecting at high sensitivity eleven asthma associated mediators: eotaxin (CCL11), granulocyte macrophage stimulating factor (GM-CSF), interferon gamma (IFNγ), interleukin-4 (IL-4), IL-5, IL-8, IL-10, IL-12 (p40), IL-13, IL-17 and tumor necrosis factor alpha (TNFα). Single cytokine levels were largely similar between asthmatic and healthy individuals when analysing asthma as single disease entity. Regulatory differences between parental and pediatric asthma were reflected by six of the eleven mediators analyzed (eotaxin, IL-4, IL-5, IL-10, IL-12, TNFα). IL-12 (p40) and IL-5 were the best predictor for extrinsic asthma in children with an increased odds ratio of 2.85 and 1.96 per log pg/ml increase (IL-12 (p40): 1.2-6.8, p=0.019, and IL-5: 1.2-2.5, p=0.025). Frequent asthma attacks in children are associated with elevated IL-5 serum levels (p=0.013). Cytokine patterns seem to be individually balanced in both, healthy and diseased adults and children, with various cytokines correlating among each other (IL-17 and IFNγ (rs=0.67), IL-4 and IL-5 (rs=0.55), IFNγ and GM-CSF (rs=0.54)).

Conclusion/significance: Our data support mainly an age- but also an asthma phenotype-dependent systemic immune regulation.

Figure 1. Box plot of serum IL-5 concentrations and asthma attack rates in one year.

Only asthmatic children (n = 443) were included in this analysis. The numbers of asthma attacks occurring in the last year were classified into continuous categories from one to four. Numbers of samples of the respective groups are 213 (group 1), 175 (group 2), 26 (group 3), and 29 (group 4). Children with the most frequent asthma attacks had the highest serum levels of IL-5 (p = 0.013).

Figure 2. Receiver operating characteristic for the diagnostic value of IL-12 (p40) (A) and IL-5 (B).

Only asthmatic children (n = 443) were included in this analysis. Area under the curve of the ROC plot produced a sensitivity of 67.1% and specificity of 66.7% for IL-12(p40), and a sensitivity of 66.5% and a specificity of 58.3% for IL-5 to distinguish between the extrinsic and intrinsic asthma phenotype.