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.