MC-released preformed mediators including chymase, tryptase, and histamine and de novo synthesized mediators such as PGD2, LTC4, and LTE4 in addition of cytokines mainly TGFβ1, TSLP, IL-33, IL-4, and IL-13 participate in pathogenesis of asthma.
Sputum IL-4, IL-5 and IL-13 protein levels did not correlate with gene expression.T2-high severe asthma can be predicted to some extent from raised levels of <i>F</i><sub>eNO</sub>, blood and sputum eosinophil counts, but serum IgE or serum periostin were poor predictors.
Androgens, via AR, blunted TNFα or IL-13-induced enhancement of ASM [Ca<sup>2+</sup>]<sub>i</sub> in both males and females, with retained efficacy in asthmatics.
The A/A genotype frequency and A allele frequency of Arg130Gln locus in IL-13 in the asthma group were obviously higher than those in the control group (54.1 vs. 17.2%, OR=6.29; 67.6 vs. 39.7%, OR=3.17, P<0.05).
Although these pathognomonic features are mainly mediated by antigen-specific Th2 cells and their cytokines, such as IL-4, IL-5, and IL-13, recent studies have revealed that other inflammatory cells, including Th17 cells and innate lymphoid cells (ILCs), also play a critical role in the pathogenesis of asthma.
Recently, new biologics targeting interleukin (IL)-5, IL-5 receptor and IL-4/IL-13, which are all cytokines involved in so-called type 2 airway inflammation, were approved for severe asthma.
Dysregulated expression of IL-13 receptor subunits in the airways of asthmatics may thus contribute to the epithelial barrier dysfunction observed in asthma.-Yang, S. J., Allahverdian, S., Saunders, A. D. R., Liu, E., Dorscheid, D. R. IL-13 signaling through IL-13 receptor α2 mediates airway epithelial wound repair.
After knocking down the lung tissue of mice, the IL-4, IL-5 and IL-13 concentrations in broncho alveolar lavage fluid of asthmatic mice were significantly decreased, and the activation of JNK1/2-MMP-9 pathway was inhibited in mouse lung tissue.
Areas covered: This review is based on recent English-language original articles in PubMed or Medline that reported significant clinical findings on the current status, therapeutic potential, and safety of biologics targeted at IL-4, IL-5, and IL-13 in the treatment of asthma together with the potential utility of simple reproducible non-invasive biomarkers to guide the effective use of biologic-based therapy that do not require direct sampling of the airways Expert commentary: The further development of reproducible and straightforward discriminatory non-invasive biomarkers may aid identification of those patients most likely to benefit from treatment with these interventions.
Mouse models of asthma have shown that much of the airway dysfunction in these models can be generated by IL-13 stimulation of the airway epithelium alone.
Persistence of experimental asthma in ST2 KO mice was associated with an increase in levels of thymic stromal lymphopoietin (TSLP), IL-9, and IL-13, but not IL-5, in bronchoalveolar lavage fluid.
In the epithelium, IL-13 response genes (POSTN, SERPINB2, and CLCA1), mast cell mediators (CPA3 and TPSAB1), inducible nitric oxide synthase, and cystatins (CST1, CST2, and CST4) were upregulated in mild asthma, but, except for cystatins, were suppressed by corticosteroids in moderate asthma.
Compared with the asthma and IgG2a mAb groups, there were less leukocytes, decreased EOS and LYM proportions, lower Underwood and PAS scores, decreased WTt, WTm, WAt/A0, WAm/WAt, WTt/R0, WTm/WTt, TSLP, OX40L, a-SMA and Collagen I mRNA and protein levels, and lower levels of SLP, OX40L, IL-4, IL-5 and IL-13, but higher MON proportions and IFN-γ levels in the anti-TSLP mAb group.
IL-13 minor T and A alleles for rs1295686 and rs20541, respectively, were associated with significantly higher risk of asthma in the Saudi Arabian population.
Asthma is generally associated with Th2 cells, which produce a panel of cytokines (IL-4, IL-5, IL-13) that act in synergy to drive lung inflammatory responses, mucus secretion, IgE production, and fibrosis, causing the characteristic symptoms of asthma.
Meta-analysis of randomized controlled trials for the efficacy and safety of anti-interleukin-13 therapy with lebrikizumab in patients with uncontrolled asthma.
As a result of their structural similarity, interleukin-13 and interleukin-4 have overlapping functions in the mediation of type-II-driven diseases and are, therefore, promising targets of biologic drugs currently in development for the treatment of such diseases, including asthma and atopic dermatitis.
Results of RT-PCR and ELISA revealed that the mRNA and protein expression levels of IL-4, IL-5, and IL-13 in lung tissues of mice in TLR2-/- asthma group were significantly decreased compared with those in C57BL/6 asthma group.