Zytokinexpression zirkulierender CD 3+ Zellen bei eosinophilen und nicht-eosinophilen Asthmatikern

Background Asthma bronchiale is one of the most common chronic diseases. For a long time, it has been considered a mainly allergy-related, TH2-mediated disease with bronchial eosino-philic inflammation. However, recently various studies were able to discover a sub-group of asthmatics with signs of non-eosinophilic inflammation, which responded poorly to therapeutical glucocorticoids. T-cells, which execute their function via ex-pressed cytokines, are commonly seen as crucial in the initiation, perpetuation and regulation of the inflammatory process. It was assumed that the expression of certain cytokines leads to the manifestation of the different phenotypes. The hypothesis of this study was that based on the profile of the cytokine expression of T-cells it could be possible to distinguish between eosinophilic and non-eosinophilic phenotypes and draw further conclusions regarding the pathogenesis of the observed differences. As the role of T-cells other than CD4+ in asthma bronchiale becomes apparent, this study focused on CD3+ T-cells. Since allergic rhinitis is considered a TH2-mediated disease as well, the exploration of similarities in the cytokine expression of CD3+ T-cells between allergic rhinitics and eosinophilic asthmatics was another goal. To address the problem of glucocorticoid resistance in asthmatics, the third objective of this study was to examine differences in the cytokine expression of the two phenotypes after an 8-week therapy with inhaled corticosteroids. Methods This study included 9 eosinophilic and 11 non-eosinophilic asthmatics, 10 patients with allergic rhinitis and 10 healthy control subjects. Apart from asthma-specific routine diagnostics, further phenotyping and an isolation of CD3+ T-cells from peripheral blood was conducted. After CD3+ T-cells were stimulated for 24 hours, the cytokine expres-sion of IL-5, IL-6, IL-10, IL-13 und IL-17A was evaluated on protein level via Cytometric Bead Array (CBA) and on RNA level via quantitative Polymerase Chain Reaction (qPCR), IL-4 was only measured on protein level. The asthmatic patients subsequently received an inhalative corticosteroid for 8 weeks after which the cytokine expression was measured again. Results In the case of interleukin 17A and interleukin 10, this study found a significant increase in the cytokine expression of asthmatics compared to healthy individuals and allergic rhinitics, whereas the increase for interleukins 5 and 13 did not reach statistical signifi-cance. Between eosinophilic and non-eosinophilic asthmatics no significant differences were discovered on protein or RNA level. The analysis of the pre-post comparison un-der Ciclesonide therapy showed a significant increase in expression over time with IL-6, however on the RNA level this increase was not reaching a statistically significant level. Conclusion The results could not demonstrate significant differences in the cytokine expression of CD3+ T-cells between eosinophilic and non-eosinophilic phenotypes. Possible reasons are the low number of participants, great phenotypic heterogeneity in the asthmatic cohorts and only a minor share of peripheral CD3+ T-cells being sensitized to asthma-related inflammation. The application of other criteria could probably be more con-structive. Possibly the analysis of cytokine-induced genes is a promising approach to find a classification that allows for individualized treatment meeting the therapeutical needs of patients. Our study indicated that therapy over 8 weeks with inhalative Ciclesonide leads to an increased expression of the proinflammatory IL-6 in CD3+ T-cells. The reasons for these findings remain speculative. A possible explanation is the susceptibility of the bronchial mucosa to viral infections due to reduced local immune defense. Furthermore, a de-crease in TH2 cells could allow previously suppressed IL-6 producing cells to express the cytokine to a higher degree. Further studies are necessary to evaluate this finding.