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Anti-IL5 Treatment Alters Eosinophil Responses to a Rhinovirus-16 Challenge in Mild Asthma Patients and Also that of Neutrophils, Macrophages and B Cells
Description
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A1196 - Anti-IL5 Treatment Alters Eosinophil Responses to a Rhinovirus-16 Challenge in Mild Asthma Patients and Also that of Neutrophils, Macrophages and B Cells
Author Block: Y. S. Sabogal Piñeros1, S. Bal1, M. A. Van De Pol1, B. Smids-Dierdorp1, T. Dekker1, A. Dijkhuis1, P. Brinkman2, K. F. Van Der Sluijs1, C. J. Majoor2, P. Bonta2, P. J. Sterk2, R. Lutter3; 1Experimental Immunology and Pulmonology, AMC, Amsterdam, Netherlands, 2Respiratory Medicine, AMC, Amsterdam, Netherlands, 3Respiratory Medicine, AMC/University of Amsterdam, Amsterdam, Netherlands.
Rationale
Eosinophils are considered major contributors to the pathophysiology in asthma and therefore treatment is focused on reducing eosinophil numbers. Mepolizumab, a humanized monoclonal antibody that neutralizes interleukin 5 (IL-5), efficiently attenuates both systemic and local eosinophils but proved clinically effective only in severe eosinophilic asthma.
Methods
To study the contribution of eosinophils to the pathophysiology in mild asthma we performed a placebo-controlled double blind trial with Mepolizumab after which patients were subjected to a rhinovirus (RV)16 challenge to induce loss of asthma control.
Results
Mepolizumab attenuated eosinophil numbers in blood and BALF and reduced their activation status in blood, BALF and sputum, but lung function and FeNO remained unaffected. Furthermore, Mepolizumab enhanced circulating NK cells at baseline. Upon RV16 challenge Mepolizumab prevented reduction of B lymphocytes and macrophages as well as the increase of neutrophils and Myeloperoxidase (MPO) release. Furthermore, Mepolizumab enhanced sIgA production and reduced tryptase in BALF. Finally, Mepolizumab affected RV16-induced MIP-3A, VEGF-A and IL-1RA production in BALF.
Conclusion
In mild asthma we found that IL-5, likely via eosinophils, drives both innate (neutrophils, macrophages, sIgA, tryptase, IL-1RA, VEGF-A and MIP-3a) and adaptive (B lymphocytes) immune responses to the RV16 challenge. These findings substantiate the pathophysiological role of IL-5 and eosinophils in mild asthma and lead to a new perspective on therapeutic benefits of reducing eosinophils in asthma.
Funding
This investigator-initiated study was supported by grants from the Dutch Lung Foundation and GSK.
Author Block: Y. S. Sabogal Piñeros1, S. Bal1, M. A. Van De Pol1, B. Smids-Dierdorp1, T. Dekker1, A. Dijkhuis1, P. Brinkman2, K. F. Van Der Sluijs1, C. J. Majoor2, P. Bonta2, P. J. Sterk2, R. Lutter3; 1Experimental Immunology and Pulmonology, AMC, Amsterdam, Netherlands, 2Respiratory Medicine, AMC, Amsterdam, Netherlands, 3Respiratory Medicine, AMC/University of Amsterdam, Amsterdam, Netherlands.
Rationale
Eosinophils are considered major contributors to the pathophysiology in asthma and therefore treatment is focused on reducing eosinophil numbers. Mepolizumab, a humanized monoclonal antibody that neutralizes interleukin 5 (IL-5), efficiently attenuates both systemic and local eosinophils but proved clinically effective only in severe eosinophilic asthma.
Methods
To study the contribution of eosinophils to the pathophysiology in mild asthma we performed a placebo-controlled double blind trial with Mepolizumab after which patients were subjected to a rhinovirus (RV)16 challenge to induce loss of asthma control.
Results
Mepolizumab attenuated eosinophil numbers in blood and BALF and reduced their activation status in blood, BALF and sputum, but lung function and FeNO remained unaffected. Furthermore, Mepolizumab enhanced circulating NK cells at baseline. Upon RV16 challenge Mepolizumab prevented reduction of B lymphocytes and macrophages as well as the increase of neutrophils and Myeloperoxidase (MPO) release. Furthermore, Mepolizumab enhanced sIgA production and reduced tryptase in BALF. Finally, Mepolizumab affected RV16-induced MIP-3A, VEGF-A and IL-1RA production in BALF.
Conclusion
In mild asthma we found that IL-5, likely via eosinophils, drives both innate (neutrophils, macrophages, sIgA, tryptase, IL-1RA, VEGF-A and MIP-3a) and adaptive (B lymphocytes) immune responses to the RV16 challenge. These findings substantiate the pathophysiological role of IL-5 and eosinophils in mild asthma and lead to a new perspective on therapeutic benefits of reducing eosinophils in asthma.
Funding
This investigator-initiated study was supported by grants from the Dutch Lung Foundation and GSK.
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