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Molecular Mechanisms Controlling Immunoglobulin E Responses
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Rachel L. Miller, Paul B. Rothman
Whereas IL-4 is critical to IgE production, another type 2 cytokine, IL-5, acts as a differentiation and growth factor for eosinophils during allergic disease. Interleukin-5, IL-3, and GM-CSF all induce eosinophil production, as demonstrated in both in vitro and in vivo experiments [44], but only IL-5 is specific for the eosinophil lineage. The IL-5 stimulates eosinophilopoiesis in the bone marrow [45] and promotes the terminal differentiation of myeloid precursors into eosinophils [46]. Eosinophils play an essential role during allergic diseases and parasitic infections by releasing eosinophil-derived proteins such as major basic protein (MBP) and the eosinophilic cationic protein (ECP). In helminthic and parasitic infections, the eosinophilie-derived granules are believed to be toxic to the infesting cells. In asthma, epithelial shedding is believed to result from the release of eosinophil major basic protein [47], and mucus hypersecretion and airway hypereactivity are believed to be consequences of the release of the eosinophil and mast cell-derived leukotriene C4, which is cleaved to the active products leukotriene D4 and E4 [48]. In addition, IL-5 promotes the migration of eosinophils from the blood to the tissues in response to antigen challenge [49,50] and increases eosinophil, but not neutrophil, adhesion to vascular endothelium [51]. Although IL-5 does not contribute to IgE production, the Th2 immune response that promotes IL4, IL-13, and IL-5 secretion, all contribute to the inflammation-related symptoms in complementary ways.
Infection and immunology
Published in Jagdish M. Gupta, John Beveridge, MCQs in Paediatrics, 2020
Jagdish M. Gupta, John Beveridge
5.35. Which of the following statements is/are correct? TH] cells produce interleukin 2 and interferon gamma.TH1 cells promote cell mediated immunity.TH2 cells secrete interleukins 4 and 5.Interleukin 4 production promotes the switching of Β cells to IgE production.Interleukin 5 promotes eosinophil growth and differentiation.
IgE-mediated (immediate) hypersensitivity
Published in Gabriel Virella, Medical Immunology, 2019
Albert F. Finn, Gabriel Virella
Role of eosinophils in the late phase. Eosinophils are attracted to the site where an immediate hypersensitivity reaction is taking place by chemotactic factors released by basophils, mast cells, and Th2 lymphocytes, including the following: ECF-A and PAF, preformed chemotactic factors released during basophil or mast cell degranulation.Leukotriene B4, synthesized and released by stimulated basophils/mast cells.Interleukin-5, released by activated Th2 lymphocytes, mast cells, and eosinophils.
Diagnostic and therapeutic approaches for elderly asthma patients: the importance of multidisciplinary and multidimensional management
Published in Expert Review of Respiratory Medicine, 2023
Alida Benfante, Alessandra Tomasello, Enrico Gianquinto, Maria Noemi Cicero, Nicola Scichilone
The peripheral eosinophilia significantly increased with chronic respiratory symptoms and hyperreactive state of older asthmatics according to Normative Aging Study [67]. In addition, it has been demonstrated that in older asthmatics IL-5 predicted the longitudinal changes in lung function [68]. Baseline variables including age were investigated as predictive of overall rate of exacerbations and of differential efficacy of Mepolizumab [69], a humanized mAB against interleukin 5 that inhibits eosinophilic airway inflammation preventing the binding of IL-5 to the IL-5 R. Covariates influencing the overall number of exacerbations were numbers of exacerbations in the year before screening, treatment, blood eosinophil count at screening and baseline maintenance oral glucocorticosteroid use. In this study, age was not reported to have any influence. Despite the wide number of adult patients (≥18 years) enrolled in the DREAM trial [70] and in the MENSA study [69], 590 (96%) and 471 adults (82%) respectively, only 25 subjects over 65 yrs (4%) in the DREAM trial and 80 (14%) in the MENSA study were enrolled. In a post-hoc analysis of the DREAM and MENSA studies by Ortega et al [71], no investigation on differences in exacerbation rate, lung functional assessment and safety assessment based on age subgroups was performed.
Results in clinical practice in the treatment of severe eosinophilic asthma with mepolizumab: a real-life study
Published in Journal of Asthma, 2022
Ana Isabel Enríquez-Rodríguez, Tamara Hermida Valverde, Pedro Romero Álvarez, Francisco Julián López-González, Jose Antonio Gullón Blanco, Ana Rosa Expósito Villegas, María José Escobar Fernández, Ana María Beristáin Urquiza, Miguel Ángel Alonso Fernández, Margarita Gutiérrez Rodríguez, Gema Castaño De las Pozas, Jennifer Jiménez Pérez, Roberto Fernández Mellado, Marta María García Clemente, Pere Casan Clara
Asthma is a chronic respiratory disease characterized by the presence of inflammation, variable airway obstruction, and bronchial hyperresponsiveness (1). Severe asthma patients require treatment with high dose inhaled corticosteroids (IC) in combination with long acting beta-agonists (LABA) and additional controllers (2). Patients with high levels of blood and/or sputum eosinophils are defined as severe asthma patients with an eosinophilic phenotype. International asthma guidelines recommend add-on biological therapy for severe eosinophilic asthma patients that remain uncontrolled despite maximal dose of an inhaled corticosteroids/long acting beta-2 agonists combination (ICS-LABA) and/or OCS. Interleukin-5 (IL-5) is the major cytokine responsible for the growth, differentiation, recruitment, activation, and survival of eosinophils. Mepolizumab, a humanized monoclonal antibody, blocks IL-5 reducing eosinophil production and survival in the airways (3,4). Mepolizumab reduced the number of exacerbations, the need of OCS and increased asthma control, health-related quality of life (HRQoL), and lung function in a population of uncontrolled severe eosinophilic asthma in clinical trials and real-life studies (5–13).
Eosinophilic pneumonia: a case of daptomycin induced lung injury
Published in Journal of Community Hospital Internal Medicine Perspectives, 2021
Vaishnavi Raman, Isha Chaudhary, Sean Shieh
To effectively assess this condition, it is important to understand the pathophysiology. One study proposed that the detection of antigens by alveolar macrophages leads to the recruitment of T-helper 2 lymphocytes and the release of interleukin 5. The function of interleukin 5 is to induce the production of eosinophils and migration to the lung. Eotaxin, an eosinophil chemoattractant, is produced by alveolar macrophages and other cells in the lungs. This substance further induces an accumulation of eosinophils. It is hypothesized that daptomycin is retained in the pulmonary surfactant and when concentrations become high enough, it can lead to injury of the surrounding tissues. This injury will then activate alveolar macrophages and initiate the process of eosinophil accumulation [12].