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    Refining anti-inflammatory therapy strategies for bronchopulmonary dysplasia

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    Author
    Rudloff, I; Cho, SX; Bui, CB; McLean, C; Veldman, A; Berger, PJ; Nold, MF; Nold-Petry, CA
    Date
    2017-06-01
    Source Title
    Journal of Cellular and Molecular Medicine
    Publisher
    WILEY
    University of Melbourne Author/s
    McLean, Catriona
    Affiliation
    Florey Department of Neuroscience and Mental Health
    Metadata
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    Document Type
    Journal Article
    Citations
    Rudloff, I., Cho, S. X., Bui, C. B., McLean, C., Veldman, A., Berger, P. J., Nold, M. F. & Nold-Petry, C. A. (2017). Refining anti-inflammatory therapy strategies for bronchopulmonary dysplasia. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 21 (6), pp.1128-1138. https://doi.org/10.1111/jcmm.13044.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/258124
    DOI
    10.1111/jcmm.13044
    Abstract
    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% O2 ) or hyperoxia (65% or 85% O2 ) 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.

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