IL-17E but not IL-17A is associated with allergic sensitization: Results from the LISA study.

Functional studies have provided evidence for the importance of IL-17A and IL-17E in the regulation of immune responses. IL-17A is involved in inflammation and IL-17E is able to induce Th2 cytokine production and eosinophilia. By now it is not clear whether these cytokines correlate with specific IgE levels. The aim of our investigation was to analyse the relationship of these two cytokines to allergic sensitization in context of an epidemiological study. Within the Life style Immune System Allergy study (LISA), we analysed phytohemagglutinin (PHA)-stimulated blood samples of 6 yr old children for the concentration of IL-17A and IL-17E and sera for levels of specific IgE. In total, data from 293 children were available for blood analysis and for the analysis of confounding factors for the allergic sensitization. Among the investigated children, 29% reacted against inhalant and 13.6% against food allergens, whereas 33.1% of children were sensitized to any allergen.IL-17E was associated with high levels of any specific IgE (adjusted odds ratio (OR) 1.45, 95% confidence interval (CI) 1.11-1.90). Furthermore, children with high IL-17E responses (>208.8 pg/ml) were sensitized to food and inhalant allergens (OR 1.45, 95% CI 1.02-2.07 and OR 1.35, 95% CI 1.03-.77, respectively) and to Der p 1 (OR 1.55, 95% CI 1.12-2.15). In contrast, IL-17A, in trend, was negatively associated to sensitization to timothy (p for trend=0.013) and rye (p for trend=0.026). Concluding IL-17E production is linked to the amount of specific IgE antibodies in blood samples of 6 yr old children

Association between suppressors of cytokine signalling, T-helper type 1/T-helper type 2 balance and allergic sensitization in children.

Suppressors of cytokine signalling (SOCS) family members have been shown to play an important role in the balance of cytokines that determine the onset of T-helper type 1 (Th1)- and Th2-mediated immune responses. In particular, for cytokine-induced Src-homology 2 protein (CIS), SOCS1, SOCS3 and SOCS5, a role in the regulation of T cell differentiation has been discussed. However, only few data exist so far in the human system. OBJECTIVES: The aim of the present study was to analyse the relationship between these suppressors and Th1/Th2 regulation as well as allergic sensitizations within a population-based study. METHODS: Within the Lifestyle-Immune system-Allergy plus cohort study, mRNA was prepared from blood samples of 6-year-old children for the analysis of cytokines, transcription factors for T cell regulation and SOCS molecule expression by quantitative real-time polymerase chain reaction. In addition, total and specific IgE concentrations have been measured by the Pharmacia CAP System. A complete data set from 248 children was available. Results Among the SOCS molecules investigated, only SOCS1 showed a strong positive correlation to allergic sensitizations. In addition, an up-regulated SOCS1 expression correlated with down-regulated T-box expressed in T cells (Tbet) and higher expression levels of GATA-binding protein 3 (GATA-3) and IL-4. No association between SOCS1 and forkhead box P3 (FOXP3) was observed. For SOCS3, SOCS5 and CIS, a contradictory picture was found. The expression of these SOCS molecules was positively correlated with Tbet and FOXP3 and (with the exception of CIS) negatively with IL-4. CONCLUSIONS: Our data suggest that SOCS3, SOCS5 and CIS, which correlate with an up-regulated Th1 and regulatory T cell activity, are without relevance for the allergic status. In contrast, SOCS1 might be involved in the development of a Th2-skewed immune response and subsequent allergic sensitizations