Upstream Regulator Analysis revealed that not only T-helper 2 (Th2) and the eosinophilia-related molecules (interleukin 4 [IL4], IL5, and colony stimulating factor 2 [CSF2]) reported so far, but also cell cycle regulators (cyclin dependent kinase inhibitor 1A [CDKNA1] and cyclin D1 [CCND1]) and a tissue fibrosis-related molecule (transforming growth factor β [TGFβ]) were identified in ECRSwNP.
Eosinophilic bronchitis is usually a Type 2 (T2)-driven process and therefore a sputum eosinophilia of greater than 3% usually indicates a response to treatment with corticosteroids or novel therapies directed against T2 cytokines such as IL-4, IL-5, and IL-13.
Combined anti-IL-4 and anti-RSV siRNAs were able to significantly reduce total cell counts and eosinophilia in bronchoalveolar lavage fluid, development of airway hyperresponsiveness, and airway inflammation and to downregulate IL-4 mRNA expression and RSV viral RNA, but to upregulate IFN-γ levels in lung tissues.
Similarly, we found that esophageal eosinophilia in IL-4/IL-13 double gene-deficient and STAT6 gene-deficient mice were also not reduced following allergen-induced experimental EoE.
Additionally, IFN-λ and IFN-β induction correlated inversely with the airway T(H)2 immunopathologic profile (eosinophilia and IL-4 positivity: P < .05 and r = -0.38 and P < .05 and r = -0.58, respectively) and with epithelial damage (P < .05 and r = -0.55).
We also reported that while IL-5 replenishment promotes reversal of eosinophilia in lungs of PARP-1(-/-) mice, IL-4 or Immunoglobulin E replenishment do not, suggesting a potentially significant regulatory relationship between PARP-1 and IL-5.
Our data suggest that secreted vvGs uses mechanisms requiring signaling through the IL-4Ralpha-chain by either IL-4 or IL-13 for induction of eosinophilia and is the first description of the relative contributions of IL-4, IL-13, and their receptors in viral pathogenesis.
The inhibitory effect on airway eosinophilia and AHR was associated with reduced levels of IL-4, IL-5, and IL-13 in the bronchoalveolar lavage fluid as well as reduced serum levels of OVA-IGE: These observations demonstrate the therapeutic potential of IL-4 mutant protein receptor antagonists that inhibit both IL-4 and IL-13 in the treatment of allergic asthma.
The effect of IP-10 expression at the time of initial Ag encounter is persistent, as mice rechallenged with OVA following the resolution of acute inflammation exhibited reduced eosinophilia and IL-4 in the BAL.
Exposure to mIL-17E resulted in a Th2-biased response, characterized by eosinophilia, increased serum IgE and IgG1, and a Th2 cytokine profile including elevated serum levels of IL-13 and IL-5 and elevated gene expression of IL-4, IL-5, IL-10, and IL-13 was observed in many tissues.
After allergen provocation in sensitive patients with atopic asthma, basophils are recruited to the bronchial mucosa and express IL-4 mRNA and protein, which might contribute to local IgE synthesis and/or tissue eosinophilia or other aspects of allergic inflammation during late responses and ongoing asthma.
Those treated with the immune complexes showed significantly higher levels of IL-4 and more pronounced eosinophilia in BAL fluid than did those receiving the Ag alone.
Lung eosinophilia was also associated with a localized reduction in IFN-gamma and increased IL-4 and IL-5 mRNA transcription as well as elevated RSV specific IgG1 antibody production.
The presence of eosinophilia in most HD patients and the presence of hyper-IgE in a subset of them may suggest that activated lymph node T cells release large amounts of IL5 and IL4, respectively.
We describe a patient whose presenting laboratory features of elevated IgG4 and IgE and eosinophilia suggested high levels of IL-4 and IL-5 and in vivo expansion of the CD4+ Th2 subset.