Anti–IL-5 in Mild Asthma Alters Rhinovirus-induced Macrophage, B-Cell, and Neutrophil Responses (MATERIAL) A Placebo-controlled, Double-Blind Study

Yanaika S. Sabogal Piñeros, Suzanne M. Bal, Marianne A. van de Pol, Barbara S. Dierdorp, Tamara Dekker, Annemiek Dijkhuis, Paul Brinkman, Koen F. van der Sluijs, Aeilko H. Zwinderman, Christof J. Majoor, Peter I. Bonta, Lara Ravanetti, Peter J. Sterk, René Lutter

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Rationale: Eosinophils drive pathophysiology in stable and exacerbating eosinophilic asthma, and therefore treatment is focused on the reduction of eosinophil numbers. Mepolizumab, a humanized monoclonal antibody that neutralizes IL-5 and efficiently attenuates eosinophils, proved clinically effective in severe eosinophilic asthma but not in mild asthma. Objectives: To study the effect of mepolizumab on virus-induced immune responses in mild asthma. Methods: Patients with mild asthma, steroid-naive and randomized for eosinophil numbers, received 750 mg mepolizumab intravenously in a placebo-controlled double-blind trial, 2 weeks after which patients were challenged with rhinovirus (RV) 16. FEV 1 , FVC, fractional exhaled nitric oxide, symptom scores (asthma control score), viral load (PCR), eosinophil numbers, humoral (luminex, ELISA), and cellular (flow cytometry) immune parameters in blood, BAL fluid, and sputum, before and after mepolizumab and RV16, were assessed. Measurements and Main Results: Mepolizumab attenuated baseline blood eosinophils and their activation, attenuated trendwise sputum eosinophils, and enhanced circulating natural killer cells. Mepolizumab did not affect FEV 1 , FVC, and fractional exhaled nitric oxide, neither at baseline nor after RV16. On RV16 challenge mepolizumab did not prevent eosinophil activation but did enhance local B lymphocytes and macrophages and reduce neutrophils and their activation. Mepolizumab also enhanced secretory IgA and reduced tryptase in BAL fluid. Finally, mepolizumab affected particularly RV16-induced macrophage inflammatory protein-3a, vascular endothelial growth factor-A, and IL-1RA production in BAL fluid. Conclusions: Mepolizumab failed to prevent activation of remaining eosinophils and changed RV16-induced immune responses in mild asthma. Although these latter effects likely are caused by attenuated eosinophil numbers, we cannot exclude a role for basophils.
Original languageEnglish
Pages (from-to)508-517
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume199
Issue number4
DOIs
Publication statusPublished - 15 Feb 2019
Externally publishedYes

Cite this

Sabogal Piñeros, Yanaika S. ; Bal, Suzanne M. ; van de Pol, Marianne A. ; Dierdorp, Barbara S. ; Dekker, Tamara ; Dijkhuis, Annemiek ; Brinkman, Paul ; van der Sluijs, Koen F. ; Zwinderman, Aeilko H. ; Majoor, Christof J. ; Bonta, Peter I. ; Ravanetti, Lara ; Sterk, Peter J. ; Lutter, René. / Anti–IL-5 in Mild Asthma Alters Rhinovirus-induced Macrophage, B-Cell, and Neutrophil Responses (MATERIAL) A Placebo-controlled, Double-Blind Study. In: American Journal of Respiratory and Critical Care Medicine. 2019 ; Vol. 199, No. 4. pp. 508-517.
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title = "Anti–IL-5 in Mild Asthma Alters Rhinovirus-induced Macrophage, B-Cell, and Neutrophil Responses (MATERIAL) A Placebo-controlled, Double-Blind Study",
abstract = "Rationale: Eosinophils drive pathophysiology in stable and exacerbating eosinophilic asthma, and therefore treatment is focused on the reduction of eosinophil numbers. Mepolizumab, a humanized monoclonal antibody that neutralizes IL-5 and efficiently attenuates eosinophils, proved clinically effective in severe eosinophilic asthma but not in mild asthma. Objectives: To study the effect of mepolizumab on virus-induced immune responses in mild asthma. Methods: Patients with mild asthma, steroid-naive and randomized for eosinophil numbers, received 750 mg mepolizumab intravenously in a placebo-controlled double-blind trial, 2 weeks after which patients were challenged with rhinovirus (RV) 16. FEV 1 , FVC, fractional exhaled nitric oxide, symptom scores (asthma control score), viral load (PCR), eosinophil numbers, humoral (luminex, ELISA), and cellular (flow cytometry) immune parameters in blood, BAL fluid, and sputum, before and after mepolizumab and RV16, were assessed. Measurements and Main Results: Mepolizumab attenuated baseline blood eosinophils and their activation, attenuated trendwise sputum eosinophils, and enhanced circulating natural killer cells. Mepolizumab did not affect FEV 1 , FVC, and fractional exhaled nitric oxide, neither at baseline nor after RV16. On RV16 challenge mepolizumab did not prevent eosinophil activation but did enhance local B lymphocytes and macrophages and reduce neutrophils and their activation. Mepolizumab also enhanced secretory IgA and reduced tryptase in BAL fluid. Finally, mepolizumab affected particularly RV16-induced macrophage inflammatory protein-3a, vascular endothelial growth factor-A, and IL-1RA production in BAL fluid. Conclusions: Mepolizumab failed to prevent activation of remaining eosinophils and changed RV16-induced immune responses in mild asthma. Although these latter effects likely are caused by attenuated eosinophil numbers, we cannot exclude a role for basophils.",
author = "{Sabogal Pi{\~n}eros}, {Yanaika S.} and Bal, {Suzanne M.} and {van de Pol}, {Marianne A.} and Dierdorp, {Barbara S.} and Tamara Dekker and Annemiek Dijkhuis and Paul Brinkman and {van der Sluijs}, {Koen F.} and Zwinderman, {Aeilko H.} and Majoor, {Christof J.} and Bonta, {Peter I.} and Lara Ravanetti and Sterk, {Peter J.} and Ren{\'e} Lutter",
year = "2019",
month = "2",
day = "15",
doi = "10.1164/rccm.201803-0461OC",
language = "English",
volume = "199",
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Sabogal Piñeros, YS, Bal, SM, van de Pol, MA, Dierdorp, BS, Dekker, T, Dijkhuis, A, Brinkman, P, van der Sluijs, KF, Zwinderman, AH, Majoor, CJ, Bonta, PI, Ravanetti, L, Sterk, PJ & Lutter, R 2019, 'Anti–IL-5 in Mild Asthma Alters Rhinovirus-induced Macrophage, B-Cell, and Neutrophil Responses (MATERIAL) A Placebo-controlled, Double-Blind Study' American Journal of Respiratory and Critical Care Medicine, vol. 199, no. 4, pp. 508-517. https://doi.org/10.1164/rccm.201803-0461OC

Anti–IL-5 in Mild Asthma Alters Rhinovirus-induced Macrophage, B-Cell, and Neutrophil Responses (MATERIAL) A Placebo-controlled, Double-Blind Study. / Sabogal Piñeros, Yanaika S.; Bal, Suzanne M.; van de Pol, Marianne A.; Dierdorp, Barbara S.; Dekker, Tamara; Dijkhuis, Annemiek; Brinkman, Paul; van der Sluijs, Koen F.; Zwinderman, Aeilko H.; Majoor, Christof J.; Bonta, Peter I.; Ravanetti, Lara; Sterk, Peter J.; Lutter, René.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 199, No. 4, 15.02.2019, p. 508-517.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Anti–IL-5 in Mild Asthma Alters Rhinovirus-induced Macrophage, B-Cell, and Neutrophil Responses (MATERIAL) A Placebo-controlled, Double-Blind Study

AU - Sabogal Piñeros, Yanaika S.

AU - Bal, Suzanne M.

AU - van de Pol, Marianne A.

AU - Dierdorp, Barbara S.

AU - Dekker, Tamara

AU - Dijkhuis, Annemiek

AU - Brinkman, Paul

AU - van der Sluijs, Koen F.

AU - Zwinderman, Aeilko H.

AU - Majoor, Christof J.

AU - Bonta, Peter I.

AU - Ravanetti, Lara

AU - Sterk, Peter J.

AU - Lutter, René

PY - 2019/2/15

Y1 - 2019/2/15

N2 - Rationale: Eosinophils drive pathophysiology in stable and exacerbating eosinophilic asthma, and therefore treatment is focused on the reduction of eosinophil numbers. Mepolizumab, a humanized monoclonal antibody that neutralizes IL-5 and efficiently attenuates eosinophils, proved clinically effective in severe eosinophilic asthma but not in mild asthma. Objectives: To study the effect of mepolizumab on virus-induced immune responses in mild asthma. Methods: Patients with mild asthma, steroid-naive and randomized for eosinophil numbers, received 750 mg mepolizumab intravenously in a placebo-controlled double-blind trial, 2 weeks after which patients were challenged with rhinovirus (RV) 16. FEV 1 , FVC, fractional exhaled nitric oxide, symptom scores (asthma control score), viral load (PCR), eosinophil numbers, humoral (luminex, ELISA), and cellular (flow cytometry) immune parameters in blood, BAL fluid, and sputum, before and after mepolizumab and RV16, were assessed. Measurements and Main Results: Mepolizumab attenuated baseline blood eosinophils and their activation, attenuated trendwise sputum eosinophils, and enhanced circulating natural killer cells. Mepolizumab did not affect FEV 1 , FVC, and fractional exhaled nitric oxide, neither at baseline nor after RV16. On RV16 challenge mepolizumab did not prevent eosinophil activation but did enhance local B lymphocytes and macrophages and reduce neutrophils and their activation. Mepolizumab also enhanced secretory IgA and reduced tryptase in BAL fluid. Finally, mepolizumab affected particularly RV16-induced macrophage inflammatory protein-3a, vascular endothelial growth factor-A, and IL-1RA production in BAL fluid. Conclusions: Mepolizumab failed to prevent activation of remaining eosinophils and changed RV16-induced immune responses in mild asthma. Although these latter effects likely are caused by attenuated eosinophil numbers, we cannot exclude a role for basophils.

AB - Rationale: Eosinophils drive pathophysiology in stable and exacerbating eosinophilic asthma, and therefore treatment is focused on the reduction of eosinophil numbers. Mepolizumab, a humanized monoclonal antibody that neutralizes IL-5 and efficiently attenuates eosinophils, proved clinically effective in severe eosinophilic asthma but not in mild asthma. Objectives: To study the effect of mepolizumab on virus-induced immune responses in mild asthma. Methods: Patients with mild asthma, steroid-naive and randomized for eosinophil numbers, received 750 mg mepolizumab intravenously in a placebo-controlled double-blind trial, 2 weeks after which patients were challenged with rhinovirus (RV) 16. FEV 1 , FVC, fractional exhaled nitric oxide, symptom scores (asthma control score), viral load (PCR), eosinophil numbers, humoral (luminex, ELISA), and cellular (flow cytometry) immune parameters in blood, BAL fluid, and sputum, before and after mepolizumab and RV16, were assessed. Measurements and Main Results: Mepolizumab attenuated baseline blood eosinophils and their activation, attenuated trendwise sputum eosinophils, and enhanced circulating natural killer cells. Mepolizumab did not affect FEV 1 , FVC, and fractional exhaled nitric oxide, neither at baseline nor after RV16. On RV16 challenge mepolizumab did not prevent eosinophil activation but did enhance local B lymphocytes and macrophages and reduce neutrophils and their activation. Mepolizumab also enhanced secretory IgA and reduced tryptase in BAL fluid. Finally, mepolizumab affected particularly RV16-induced macrophage inflammatory protein-3a, vascular endothelial growth factor-A, and IL-1RA production in BAL fluid. Conclusions: Mepolizumab failed to prevent activation of remaining eosinophils and changed RV16-induced immune responses in mild asthma. Although these latter effects likely are caused by attenuated eosinophil numbers, we cannot exclude a role for basophils.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/30192638

U2 - 10.1164/rccm.201803-0461OC

DO - 10.1164/rccm.201803-0461OC

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SP - 508

EP - 517

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

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