Cytokines in Severe Childhood Asthma

Background Childhood asthma can be divided into distinct endotypes characterized by different immune phenotypes and cytokine profiles. Recent data confirmed this also for severe asthma. To improve and individualize the treatment of severe asthma, which is substantial to ease the burden of this life-threatening disease, a better characterization of the underlying immune mechanisms is critical.

Objectives We aimed to characterize severe asthma in children by functional analysis of cytokine secretion to identify potential new targets involved in immune regulation.

Methods Based on the Munich cross-sectional childhood asthma study (age 4-17y), n=7 severe asthmatics (SA), n=41 mild-to-moderate asthmatics (MMA), and n=21 healthy controls (HC) were selected. Peripheral blood mononuclear cells (PBMCs) were kept unstimulated or stimulated with Lipid A (LpA) or anti-CD3/CD28 for 48 hours. Cytokine levels were measured in supernatants of PBMCs with the Human Cytokine-Multiplex-Assay-Kit (Bio-Rad) by using the LUMINEX technology, with a total of n=207 measurements. Statistical analysis was performed by linear regression, adjusted for sex, BMI and age.

Results IP-10 (Interferon-γ-inducible protein 10) was significantly lower in SA as compared to MMA after stimulation with LpA (p<0.01). Furthermore, LpA-stimulated IL-17 (Interleukin 17) was significantly higher in SA compared to HC (p<0.01), but was not-significantly increased in MMA versus HC (p<0.05).

Conclusion Levels of immune biomarkers such as IP-10 and IL-17 differ distinctly between severe asthmatic and healthy children and between severe and mild-to-moderate asthma. The IL-17 associated immune-pathway may be relevant for asthma severity and decreased IP-10 secretion may point to impaired IFN-responses. Both IL-17 and IP-10 as early biomarkers during immune maturation will be further examined for their role in the pathogenesis of severe asthma.

Publikationsverlauf

Artikel online veröffentlicht:
09. März 2023