This is particularly important given recent completed and ongoing clinical trials with IL-1 biologics that have had varying degrees of failure and success as therapeutics for disease modification in asthma and COPD.
Here, we show that IL-1α and IL-1β are elevated in both bronchoalveolar lavage fluid and sputum from human asthmatics sensitized to fungi, implicating an association with IL-1α, IL-1β, or IL-1RA in fungal asthma severity.
Here, we demonstrate the release of the alarmin IL-1α after ozone exposure and that the acute respiratory barrier injury and inflammation and airway hyperreactivity are IL-1α-dependent.
IL-1 receptor appears to be a marker of neutrophilic inflammation and airflow obstruction in patients with asthma, who have a wide range of disease severity.
The aim of this study was to investigate if IL-1α and β polymorphism is associated with asthma in a pediatric population and if the genotype affects its serum level.
Thus, our study identifies caspase-8 as a master regulator of IL-1 cytokines that contribute to the pathogenesis of asthma and implicates caspase-8 inhibition as a potential therapeutic strategy for asthmatic patients.
We evidenced a new locus in the 16q12 region (near cylindromatosis turban tumor syndrome gene [CYLD]) and confirmed 4 asthma risk regions: 2q12 (IL-1 receptor-like 1 [IL1RL1]), 6p21 (HLA-DQA1), 9p24 (IL33), and 17q12-q21 (zona pellucida binding protein 2 [ZPBP2]-gasdermin A [GSDMA]).
Microbial adhesion (virulence) and Proteobacteria abundance were significantly associated with variation in the expression of the upstream regulator IL1A; suggesting that microbiome characteristics modulate host inflammatory and immune systems during asthma.
The most recent work in systems biology and asthma has occurred in the area of genomics (e.g., pharmacogenomics and gene-environment interactions), protein interaction networks [e.g., interleukin (IL)-33/IL-1 receptor-like 1 signaling], cluster analysis of asthma patients (e.g., application of severe asthma research program clusters to a general urban asthma population), and multiscale approaches to asthma encompassing data from the molecule to whole organ (e.g., modeling of airways hyperresponsiveness).
IL-33 is a nuclear cytokine from the IL-1 family constitutively expressed in epithelial barrier tissues and lymphoid organs, which plays important roles in type-2 innate immunity and human asthma.
In 2 birth cohorts, the Prevalence and Incidence of Asthma and Mite Allergy (PIAMA) study and Avon Longitudinal Study of Parents and Children (ALSPAC), we analyzed associations of longitudinal wheezing phenotypes and asthma with single nucleotide polymorphisms (SNPs) of 8 genes encoding IL-33, IL1RL1, its coreceptor IL1RAcP, its adaptors myeloid differentiation primary response gene 88 (MyD88) and Toll-IL-11 receptor domain containing adaptor protein (TIRAP), and the downstream IL-1 receptor-associated kinase 1, IL-1 receptor-associated kinase 4, and TNF receptor-associated factor 6 (TRAF6).
Interleukin-33 is an IL-1 family cytokine which signals via its T1/ST2 receptor, and acts as a key regulator of inflammation, notably the type-2 response implicated in asthma.
Global gene expression profiling of APM treated HBE activated genes related to xenobiotic metabolism (CYP 1B1), endogenous ROS generation and response genes (DUOX1, SOD2, PTGS2) and pro-inflammatory responses associated with asthma or COPD such as IL-1α, IL-1β, IL-8, and CCL20.
The discovery that the IL-1RI-IL-1 and ST2-IL-33 pathways are crucial for allergic inflammation has raised interest in these receptors as potential targets for developing new therapeutic strategies for bronchial asthma.
IL-33 is a recently characterized IL-1 family cytokine and found to be expressed in inflammatory diseases, including severe asthma and inflammatory bowl disease.
This study was performed to investigate the relationship between polymorphisms of IL-1beta promoter region -511C/T and IL-1 receptor antagonist (IL-1Ra) gene (IL-RN) and bronchial asthma in Turkish children.