Cargando…
Refining anti‐inflammatory therapy strategies for bronchopulmonary dysplasia
Bronchopulmonary dysplasia (BPD) is a severe lung disease of preterm infants, which is characterized by fewer, enlarged alveoli and increased inflammation. BPD has grave consequences for affected infants, but no effective and safe therapy exists. We previously showed that prophylactic treatment with...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431131/ https://www.ncbi.nlm.nih.gov/pubmed/27957795 http://dx.doi.org/10.1111/jcmm.13044 |
_version_ | 1783236372118634496 |
---|---|
author | Rudloff, Ina Cho, Steven X. Bui, Christine B. McLean, Catriona Veldman, Alex Berger, Philip J. Nold, Marcel F. Nold‐Petry, Claudia A. |
author_facet | Rudloff, Ina Cho, Steven X. Bui, Christine B. McLean, Catriona Veldman, Alex Berger, Philip J. Nold, Marcel F. Nold‐Petry, Claudia A. |
author_sort | Rudloff, Ina |
collection | PubMed |
description | Bronchopulmonary dysplasia (BPD) is a severe lung disease of preterm infants, which is characterized by fewer, enlarged alveoli and increased inflammation. BPD has grave consequences for affected infants, but no effective and safe therapy exists. We previously showed that prophylactic treatment with interleukin‐1 receptor antagonist (IL‐1Ra) prevents murine BPD induced by perinatal inflammation and hyperoxia. Here, we used the same BPD model to assess whether an alternative anti‐inflammatory agent, protein C (PC), is as effective as IL‐1Ra against BPD. We also tested whether delayed administration or a higher dose of IL‐1Ra affects its ability to ameliorate BPD and investigated aspects of drug safety. Pups were reared in room air (21% O(2)) or hyperoxia (65% or 85% O(2)) and received daily injections with vehicle, 1200 IU/kg PC, 10 mg/kg IL‐1Ra (early or late onset) or 100 mg/kg IL‐1Ra. After 3 or 28 days, lung and brain histology were assessed and pulmonary cytokines were analysed using ELISA and cytokine arrays. We found that PC only moderately reduced the severe impact of BPD on lung structure (e.g. 18% increased alveolar number by PC versus 34% by IL‐1Ra); however, PC significantly reduced IL‐1β, IL‐1Ra, IL‐6 and macrophage inflammatory protein (MIP)‐2 by up to 89%. IL‐1Ra at 10 mg/kg prevented BPD more effectively than 100 mg/kg IL‐1Ra, but only if treatment commenced at day 1 of life. We conclude that prophylactic low‐dose IL‐1Ra and PC ameliorate BPD and have potential as the first remedy for one of the most devastating diseases preterm babies face. |
format | Online Article Text |
id | pubmed-5431131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54311312017-06-01 Refining anti‐inflammatory therapy strategies for bronchopulmonary dysplasia Rudloff, Ina Cho, Steven X. Bui, Christine B. McLean, Catriona Veldman, Alex Berger, Philip J. Nold, Marcel F. Nold‐Petry, Claudia A. J Cell Mol Med Original Articles Bronchopulmonary dysplasia (BPD) is a severe lung disease of preterm infants, which is characterized by fewer, enlarged alveoli and increased inflammation. BPD has grave consequences for affected infants, but no effective and safe therapy exists. We previously showed that prophylactic treatment with interleukin‐1 receptor antagonist (IL‐1Ra) prevents murine BPD induced by perinatal inflammation and hyperoxia. Here, we used the same BPD model to assess whether an alternative anti‐inflammatory agent, protein C (PC), is as effective as IL‐1Ra against BPD. We also tested whether delayed administration or a higher dose of IL‐1Ra affects its ability to ameliorate BPD and investigated aspects of drug safety. Pups were reared in room air (21% O(2)) or hyperoxia (65% or 85% O(2)) and received daily injections with vehicle, 1200 IU/kg PC, 10 mg/kg IL‐1Ra (early or late onset) or 100 mg/kg IL‐1Ra. After 3 or 28 days, lung and brain histology were assessed and pulmonary cytokines were analysed using ELISA and cytokine arrays. We found that PC only moderately reduced the severe impact of BPD on lung structure (e.g. 18% increased alveolar number by PC versus 34% by IL‐1Ra); however, PC significantly reduced IL‐1β, IL‐1Ra, IL‐6 and macrophage inflammatory protein (MIP)‐2 by up to 89%. IL‐1Ra at 10 mg/kg prevented BPD more effectively than 100 mg/kg IL‐1Ra, but only if treatment commenced at day 1 of life. We conclude that prophylactic low‐dose IL‐1Ra and PC ameliorate BPD and have potential as the first remedy for one of the most devastating diseases preterm babies face. John Wiley and Sons Inc. 2016-12-13 2017-06 /pmc/articles/PMC5431131/ /pubmed/27957795 http://dx.doi.org/10.1111/jcmm.13044 Text en © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Rudloff, Ina Cho, Steven X. Bui, Christine B. McLean, Catriona Veldman, Alex Berger, Philip J. Nold, Marcel F. Nold‐Petry, Claudia A. Refining anti‐inflammatory therapy strategies for bronchopulmonary dysplasia |
title | Refining anti‐inflammatory therapy strategies for bronchopulmonary dysplasia |
title_full | Refining anti‐inflammatory therapy strategies for bronchopulmonary dysplasia |
title_fullStr | Refining anti‐inflammatory therapy strategies for bronchopulmonary dysplasia |
title_full_unstemmed | Refining anti‐inflammatory therapy strategies for bronchopulmonary dysplasia |
title_short | Refining anti‐inflammatory therapy strategies for bronchopulmonary dysplasia |
title_sort | refining anti‐inflammatory therapy strategies for bronchopulmonary dysplasia |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431131/ https://www.ncbi.nlm.nih.gov/pubmed/27957795 http://dx.doi.org/10.1111/jcmm.13044 |
work_keys_str_mv | AT rudloffina refiningantiinflammatorytherapystrategiesforbronchopulmonarydysplasia AT chostevenx refiningantiinflammatorytherapystrategiesforbronchopulmonarydysplasia AT buichristineb refiningantiinflammatorytherapystrategiesforbronchopulmonarydysplasia AT mcleancatriona refiningantiinflammatorytherapystrategiesforbronchopulmonarydysplasia AT veldmanalex refiningantiinflammatorytherapystrategiesforbronchopulmonarydysplasia AT bergerphilipj refiningantiinflammatorytherapystrategiesforbronchopulmonarydysplasia AT noldmarcelf refiningantiinflammatorytherapystrategiesforbronchopulmonarydysplasia AT noldpetryclaudiaa refiningantiinflammatorytherapystrategiesforbronchopulmonarydysplasia |