Pulmonary biology of anti-interleukin 5 antibodies

Rw, Egan; Athwahl, Diljeet; Cc, Chou; Rw, Chapman; Emtage, Spencer; Ch, Jenh; Tt, Kung; Pj, Mauser; Nj, Murgolo; Mw, Bodmer

doi:10.1590/s0074-02761997000800011

Cited by 24 publications

(12 citation statements)

References 4 publications

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“…provocation, at a time when eosinophil numbers in the bone marrow are decreasing. This suggests an active recruitment of mature eosinophils from the bone marrow to the nasal mucosa during the effector phase of the immune response to OVA 21,22 . Interestingly, nasal mucosal CD4 + lymphocytes accumulated later than eosinophils, while CD34 + cells in the bone marrow increased to a peak at 4 hr postchallenge.…”

Section: Discussionmentioning

confidence: 94%

Allergen‐induced murine upper airway inflammation: local and systemic changes in murine experimental allergic rhinitis

et al. 2001

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SUMMARYThe role of in¯ammatory effector cells in the pathogenesis of airway allergy has been the subject of much investigation. However, whether systemic factors are involved in the development of local responses in both upper and lower airways has not been fully clari®ed. The present study was performed to investigate aspects of the pathogenesis of isolated allergic rhinitis in a murine model sensitized to ovalbumin (OVA). Both upper-and lower-airway physiological responsiveness and in¯ammatory changes were assessed, as well as bone marrow progenitor responses, by culture and immunohistological methods. Signi®cant nasal symptoms and hyper-responsiveness appeared after intranasal OVA challenge (P<0 . 0001 and P<0 . 01, respectively), accompanied with signi®-cant nasal mucosal changes in CD4+ cells (P<0 . 001), interleukin (IL)-4 + cells (P<0 . 01), IL-5 + cells (P<0 . 01), basophilic cells (P<0 . 02) and eosinophils (P<0 . 001), in the complete absence of hyper-responsiveness or in¯ammatory changes in the lower airway. In the bone marrow, there were signi®cant increases in CD34 + cells, as well as in eosinophils and basophilic cells. In the presence in vitro of mouse recombinant IL-5, IL-3 or granulocyte±macrophage colony-stimulating factor (GM-CSF), the level of bone marrow eosinophil/basophil (Eo/Baso) colony-forming cells increased signi®cantly in the OVA-sensitized group. We conclude that, in this murine model of allergic rhinitis, haemopoietic progenitors are upregulated, which is consistent with the involvement of bone marrow in the pathogenesis of nasal mucosal in¯ammation. Both local and systemic events, initiated in response to allergen provocation, may be required for the pathogenesis of allergic rhinitis. Understanding these events and their regulation could provide new therapeutic targets for rhinitis and asthma.

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Section: Discussionmentioning

confidence: 94%

Allergen‐induced murine upper airway inflammation: local and systemic changes in murine experimental allergic rhinitis

et al. 2001

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“…The discovery of interleukin (IL)-5 in the 1980s as the most crucial cytokine in the regulation of growth and terminal differentiation of the eosinophil (8,9) led to major pharmaceutical investments aimed at antagonizing IL-5 with a view to blocking the eosinophil influx into the tissue and presumably inhibiting its associated sequelae. Animal models, particularly simian, pointed optimistically to such a possibility (10). However, clinical trials with a humanized anti-IL-5 monoclonal antibody, Mepolizumab, concluded that targeting the eosinophil is far more complex than blocking its differentiation at the level of the bone marrow and blood (11).…”

mentioning

confidence: 99%

The rise of the phoenix: the expanding role of the eosinophil in health and disease

Adamko

Odemuyiwa

Vethanayagam

et al. 2004

Allergy

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We have entered a new phase in the evolution of our understanding of the role of the eosinophil with a greater appreciation of novel potential functions that may be ascribed to this enigmatic cell type. This review not only provides an update to our current understanding of the various immunobiological roles for the eosinophil, but also attracts attention to some novel observations predicting functions beyond its putative effector role. These observations include the intriguing possibility that the eosinophil may posses the capacity to regulate the immune and inflammatory responses in diseases such as asthma.

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“…Early animal models showed promise with appropriate inhibition of eosinophilic-driven inflammation. For example, Egan et al19 were able to show a significant reduction in eosinophil counts in monkeys, mice, and guinea pigs on allergic experimental models after a single dose of reslizumab. Importantly, in these experiments, the effects appeared to last at least 6 months 19,20…”

Section: Reslizumabmentioning

confidence: 99%

Reslizumab in the management of poorly controlled asthma: the data so far

Maselli¹,

Velez²,

Rogers³

2016

JAA

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Interleukin-5, an important cytokine in the pathophysiology of asthma, participates in terminal maturation and increases chemotaxis, endothelial adhesion, and activation of eosinophils. Blockade of interleukin-5 activity with monoclonal antibodies have been successful in decreasing eosinophil counts. Reslizumab, a monoclonal antibody that targets interleukin-5, has been studied for the treatment of severe asthma. Several studies have shown that reslizumab can effectively treat severe asthma with an eosinophilic phenotype. Compared to placebo, patients treated with reslizumab had a reduction in the rates of asthma exacerbations and experienced improvement in FEV1 and asthma control questionnaires scores as early as 4 weeks after the therapy was initiated. Reslizumab was not effective in various asthma outcomes in patients without eosinophilia. The adverse events reported were similar in both treatment and placebo groups. Patients should be observed immediately after treatment because anaphylaxis may occur rarely (0.3%) after exposure to reslizumab. Future surveillance studies are still needed to establish the risks of malignancy and safety during pregnancy.

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Pulmonary biology of anti-interleukin 5 antibodies

Cited by 24 publications

References 4 publications

Allergen‐induced murine upper airway inflammation: local and systemic changes in murine experimental allergic rhinitis

Allergen‐induced murine upper airway inflammation: local and systemic changes in murine experimental allergic rhinitis

The rise of the phoenix: the expanding role of the eosinophil in health and disease

Reslizumab in the management of poorly controlled asthma: the data so far

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