Interleukin-13 in Asthma and Other Eosinophilic Disorders

Abstract

Asthma is characterized by episodic, reversible airflow obstruction associated with variable levels of inflammation. Over the past several decades, there has been an increasing appreciation that the clinical presentation of asthma comprises a diverse set of underlying pathologies. Rather than being viewed as a single disease entity, asthma is now thought of as a clinical syndrome with the involvement of multiple pathological mechanisms. While it is appreciated that eosinophilia is present in only a subset of patients, it remains a key feature of asthma and other eosinophilic disorders such as atopic dermatitis, eosinophilic esophagitis, and chronic rhinosinusitis with nasal polyps. Eosinophils are bone marrow-derived leukocytes present in low numbers in health; however, during disease the type 2 cytokines [interleukins (IL)-4, -5, and -13] can induce rapid eosinophilopoiesis, prolonged eosinophil survival, and trafficking to the site of injury. In diseases such as allergic asthma there is an aberrant inflammatory response leading to eosinophilia, tissue damage, and airway pathology. IL-13 is a pleiotropic type 2 cytokine that has been shown to be integral in the pathogenesis of asthma and other eosinophilic disorders. IL-13 levels are elevated in animal models of eosinophilic inflammation and in the blood and tissue of patients diagnosed with eosinophilic disorders. IL-13 signaling elicits many pathogenic mechanisms including the promotion of eosinophil survival, activation, and trafficking. Data from preclinical models and clinical trials of IL-13 inhibitors in patients have revealed mechanistic insights into the role of this cytokine in driving eosinophilia. Promising results from clinical trials further support a key mechanistic role of IL-13 in asthma and other eosinophilic disorders. Here, we provide a perspective on the role of IL-13 in asthma and other eosinophilic disorders and describe ongoing clinical trials targeting this pathway in patients with significant unmet medical needs.

Serum levels of epithelial‐derived mediators and interleukin‐4/interleukin‐13 signaling after bronchial challenge with Dermatophagoides pteronyssinus in patients with allergic asthma

“…IL‐13 is essential for the differentiation and hyperplasia stimulation of precursor cells, the activation of fibroblasts, an increase of bronchial hyperreactivity and hypersecretion of mucus, as well as being considered the central IgE synthesis regulator. IL‐13 has a number of pro‐ and anti‐inflammatory properties and correlates with peripheral blood eosinophil count …”

Protective Effect of S-Allyl Cysteine Against Neonatal Asthmatic Rats

“…We observed an increase in the expression of IL-13 in the BALF, peripheral blood, mast cells in the OVAinduced asthmatic animals and is responsible for the in ammation in the airway, remodeling and acute hyperresponsiveness (Wills-Karp et al 1998;Zhu et al 1999). IL-13 plays a major role in the pathogenesis of acute hyper-responsiveness (Brightling et al 2003;Berry et al 2004) by increasing the mucous secretion through goblet cell metaplasia (Doran et al 2017). Such observation has well correlated with the number of eosinophils observed in the asthmatic animals, without treatment, that are having airway in ammation (Truyen et al 2006) as overexpression of IL-13 is very important for the survival of eosinophils, their activation (Doran et al 2017) and for chemotaxis the eosinophils to the site of in amed or damaged airway tissues (Wynn 2003).…”

“…IL-13 plays a major role in the pathogenesis of acute hyper-responsiveness (Brightling et al 2003;Berry et al 2004) by increasing the mucous secretion through goblet cell metaplasia (Doran et al 2017). Such observation has well correlated with the number of eosinophils observed in the asthmatic animals, without treatment, that are having airway in ammation (Truyen et al 2006) as overexpression of IL-13 is very important for the survival of eosinophils, their activation (Doran et al 2017) and for chemotaxis the eosinophils to the site of in amed or damaged airway tissues (Wynn 2003). Our OVA-induced animal models showed the eosinophil in ltration, airway in ammation, mucus secretion, and hyperresponsiveness which were not observed with the SAC-co-administered OVA models.…”

Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases (RE-TREAD)

“…Several biomarkers have been developed to characterize type 2/eosinophilic inflammation in asthma, including fractional exhaled nitric oxide (FeNO), and serum or plasma periostin protein levels . These biomarkers correlate with eosinophilic airway inflammation in asthma, but have not been explored more broadly in EADs.…”

“…This eosinophil-related gene signature metric is neither age dependent nor lab dependent and may capture activation states as well as proportions of eosinophils in a peripheral blood sample. The applicability of this metric to other EADs remains to be seen.Several biomarkers have been developed to characterize type 2/eosinophilic inflammation in asthma, including fractional exhaled nitric oxide (FeNO), and serum or plasma periostin protein levels 86. These biomarkers correlate with eosinophilic airway inflammation in asthma, but have not been explored more broadly in EADs.…”