Mepolizumab for Prednisone-Dependent Asthma with Sputum Eosinophilia

Nair, Parameswaran; Pizzichini, M.M.M.; Kjarsgaard, Melanie; Inman, Mark D.; Efthimiadis, A.; Pizzichini, Emílio; Hargreave, Frederick E.; O'Byrne, Paul M.

doi:10.1056/nejmoa0805435

Cited by 1,265 publications

(948 citation statements)

References 12 publications

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“…IL-5 is a potent therapeutic target due to its causative relationship to eosinophilia. Therapies for asthma targeting IL-5 are currently being re-evaluated, and promising results have been obtained (47)(48)(49)(50). Therefore, innate IL-5-producing cells should be preferable candidates to study allergic diseases.…”

Section: Discussionmentioning

confidence: 99%

Identification of Innate IL-5–Producing Cells and Their Role in Lung Eosinophil Regulation and Antitumor Immunity

Ikutani

Yanagibashi

Ogasawara

et al. 2012

The Journal of Immunology

273

208

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IL-5 is involved in a number of immune responses such as helminth infection and allergy. IL-5 also plays roles in innate immunity by maintaining B-1 B cells and mucosal IgA production. However, the identity of IL-5–producing cells has not been unambiguously characterized. In this report, we describe the generation of an IL-5 reporter mouse and identify IL-5–producing non-T lymphoid cells that reside in the intestine, peritoneal cavity, and lungs in naive mice. They share many characteristics with natural helper cells, nuocytes, and Ih2 cells, including surface Ags and responsiveness to cytokines. However, these phenotypes do not completely overlap with any particular one of these cell types. Innate non-T IL-5–producing cells localized most abundantly in the lung and proliferated and upregulated IL-5 production in response to IL-25 and IL-33. IL-33 was more effective than IL-25. These cells contribute to maintaining sufficient numbers of lung eosinophils and are important for eosinophil recruitment mediated by IL-25 and IL-33. Given that eosinophils are shown to possess antitumor activity, we studied lung tumor metastasis and showed that innate IL-5–producing cells were increased in response to tumor invasion, and their regulation of eosinophils is critical to suppress tumor metastasis. Genetic blockade or neutralization of IL-5 impaired eosinophil recruitment into the lung and resulted in increased tumor metastasis. Conversely, exogenous IL-5 treatment resulted in suppressed tumor metastasis and augmented eosinophil infiltration. These newly identified innate IL-5–producing cells thus play a role in tumor surveillance through lung eosinophils and may contribute to development of novel immunotherapies for cancer.

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Section: Discussionmentioning

confidence: 99%

Identification of Innate IL-5–Producing Cells and Their Role in Lung Eosinophil Regulation and Antitumor Immunity

Ikutani

Yanagibashi

Ogasawara

et al. 2012

The Journal of Immunology

273

208

View full text Add to dashboard Cite

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“…Wenzel and colleagues first described this 'eosinophil high' severe asthma phenotype when performing bronchial biopsies and showed that it was associated with airway remodeling and risk of near-fatal asthma attacks [15]. Others showed that severe eosinophilic asthma is characterized by frequent exacerbations and often requires systemic corticosteroid treatment for control of the disease [14,16,17]. Persistent airway eosinophilia (with or without neutrophils) is the key characteristic of this asthma subphenotype, which appears to be reasonably stable over time [18].…”

Section: How Is Eosinophilic Asthma Defined?mentioning

confidence: 99%

Improving the diagnosis of eosinophilic asthma

Coumou

Bel

2016

Expert Review of Respiratory Medicine

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“…With regard to (sub-) phenotypes, there are indications that anti-IL-5 therapy can lead to moderate improvement in lung function tests and reduced incidence of severe exacerbation in patients with uncontrolled, eosinophilic asthma (54,55), and possibly nasal polyps (56).…”

Section: (Failure Of) Targeted Therapiesmentioning

confidence: 99%

Asthma phenotyping, therapy, and prevention: what can we learn from systems biology?

et al. 2013

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Mepolizumab for Prednisone-Dependent Asthma with Sputum Eosinophilia

Abstract: Mepolizumab reduced the number of blood and sputum eosinophils and allowed prednisone sparing in patients who had asthma with sputum eosinophilia despite prednisone treatment. (ClinicalTrials.gov number, NCT00292877.)

Cited by 1,265 publications

References 12 publications

Identification of Innate IL-5–Producing Cells and Their Role in Lung Eosinophil Regulation and Antitumor Immunity

Identification of Innate IL-5–Producing Cells and Their Role in Lung Eosinophil Regulation and Antitumor Immunity

Improving the diagnosis of eosinophilic asthma

Asthma phenotyping, therapy, and prevention: what can we learn from systems biology?

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