The relative levels of miR-126 and IL-4 and the Th17 cell percentage were positively correlated with the severity of the asthma, while IFN-γ levels and the CD4<sup>
Their Global Initiative for Asthma⁻based asthma severity, Childhood Asthma Control Test (C-ACT) scores, Pediatric Asthma Severity Scores, Pediatric Asthma Quality of Life Questionnaire scores, peak expiratory flow rates (PEFRs), medication use, the levels of immune biomarkers (immunoglobulin E (IgE), interferon γ, interleukin 4, and tumor necrosis factor α) at different visits, and the associated changes were evaluated.
Asthma is an allergic inflammation driven by the Th2 immune response with release of cytokines such as IL-4 and IL-13, which contribute to the airflow limitations and airway hyperresponsiveness (AHR).
Further, low-dose LPS (1 ug) exposure was associated with increased Th1 cytokines, T-bet, Treg cytokine (IL-10, TGF-β), and Foxp3 expression, but decreased Th2 cytokines (IL-4,5,13), GATA3, Th17, and ROR-gt expression compared with the asthma group.
Previous studies have established that expression of experimental and human asthma requires the IL-4/IL-13/IL-4 receptor α (IL-4Rα) signaling pathway, which activates the transcription factor STAT6.
We sought to target simultaneously the IL-4, IL-13, and IL-5 signaling pathways with a novel IL-4Rα/IL-5-bispecific antibody in a murine house dust mite (HDM) model of asthma.
NLRP3, but not the inflammasome adaptor ASC or caspase-1, promoted the polarization of M2 macrophages through up-regulating the expression of IL-4, thereby contributing to its regulation of 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.
Interleukin-4 (IL-4) is one of the main inflammatory cytokines that activates Th2-dependent immune response and its increased expression was observed in the course of diseases characterized by chronic low-grade systemic inflammation such as obesity and asthma.
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.
In comparison with that in the healthy control (HC), significantly lower abundance of Bifidobacterium and lower levels of Th1 cytokines (IFN-γ and TNF-α), but higher levels of Th2-type cytokines (IL-4, IL-5) and Th17-type (IL-17A) cytokine were detected in children with bronchiolitis and asthma.
No biologic targeting the IL-4/IL-13 pathway is currently available for treatment of asthma, but emerging data suggest that biologics targeting IL-4 and IL-13 together may benefit patients with T2 high asthma.
The pooled data revealed that the proportion of children with fewer episodes of asthma was significantly higher in the probiotics group than in the control group (risk ratio 1.3, 95% confidence interval (CI) 1.06-1.59); the reduction of IL-4 (mean differences -2.34, 95% CI -3.38, -1.29) and the increasing of interferon-γ (mean differences 2.5, 95% CI 1.23-3.76) was also significant after the treatment of probiotics.
In CD4+ T cells treated with PMA+MLIF, the expression levels of IFN-γ, TNF-α and IL-4 were strongly inhibited (p<0.001, p<0.001 and p<0.0094), compared to PMA treatment alone, for both, rhinitis and asthma.
Therefore the development of inhibitors that specifically modulate IL-13/IL-4 or the downstream signaling molecules like Stat6 may be useful as a therapeutic strategy for the treatment of asthma and multiple allergic diseases.
In addition, INF-γ expression was decreased and IL-4 increased in the asthma and asthma with smoke exposure groups compared with the control group (P<0.01), and in the asthma with smoke exposure group compared with the asthma group (P<0.01).
Inhibition of IL-13 and IL-4 with mabs may be more encouraging and patients will probably have additional benefits from these therapeutic interventions because of IL-13/IL-4 overlapping actions in asthma pathophysiology.
Compared with the asthma group, the IL-4R group had relatively regular tissue structure and light inflammation, declined maximal RL, numbers of total cells, EOS, neutrophils, and lymphocytes, contents of IgE, IL-4, IL-5 and IL-13, percentages of IFN-γ<sup>+</sup> CD4<sup>+</sup> and IFN-γ<sup>+</sup>/IL-4<sup>+</sup> in total T cells, mRNA expressions of IL-4, IL-5, IL-13, STAT6, pSTAT6, SOCS, iNOS and VCAM-1, and protein expressions of STAT6 and pSTAT6, but elevated IFN-γ content and percentage of IL-4<sup>+</sup> CD4<sup>+</sup> in total T cells.