Interleukin-1 receptor antagonist prevents murine bronchopulmonary dysplasia induced by perinatal inflammation and hyperoxia
| Autor: | Thilini Samarasinghe, Alex Veldman, Niamh E. Mangan, Steven X. Cho, Ina Rudloff, John Pedersen, Nikeh Shariatian, Elizabeth M. Skuza, Marcel F. Nold, Philip J. Berger, Claudia A. Nold-Petry |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Lipopolysaccharides
Population Inflammation Hyperoxia Biology Proinflammatory cytokine Mice Pregnancy medicine Animals Humans education Lung Macrophage inflammatory protein Bronchopulmonary Dysplasia education.field_of_study Multidisciplinary Infant Newborn Biological Sciences medicine.disease Mice Inbred C57BL Disease Models Animal Interleukin 1 Receptor Antagonist Protein medicine.anatomical_structure Interleukin 1 receptor antagonist Bronchopulmonary dysplasia Immunology Female medicine.symptom |
| Zdroj: | Proceedings of the National Academy of Sciences. 110:14384-14389 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1306859110 |
| Popis: | Bronchopulmonary dysplasia (BPD) is a common lung disease of premature infants, with devastating short- and long-term consequences. The pathogenesis of BPD is multifactorial, but all triggers cause pulmonary inflammation. No therapy exists; therefore, we investigated whether the anti-inflammatory interleukin-1 receptor antagonist (IL-1Ra) prevents murine BPD. We precipitated BPD by perinatal inflammation (lipopolysaccharide injection to pregnant dams) and rearing pups in hyperoxia (65% or 85% O 2 ). Pups were treated daily with IL-1Ra or vehicle for up to 28 d. Vehicle-injected animals in both levels of hyperoxia developed a severe BPD-like lung disease (alveolar number and gas exchange area decreased by up to 60%, alveolar size increased up to fourfold). IL-1Ra prevented this structural disintegration at 65%, but not 85% O 2 . Hyperoxia depleted pulmonary immune cells by 67%; however, extant macrophages and dendritic cells were hyperactivated, with CD11b and GR1 (Ly6G/C) highly expressed. IL-1Ra partially rescued the immune cell population in hyperoxia (doubling the viable cells), reduced the percentage that were activated by up to 63%, and abolished the unexpected persistence of IL-1α and IL-1β on day 28 in hyperoxia/vehicle-treated lungs. On day 3, perinatal inflammation and hyperoxia each triggered a distinct pulmonary immune response, with some proinflammatory mediators increasing up to 20-fold and some amenable to partial or complete reversal with IL-1Ra. In summary, our analysis reveals a pivotal role for IL-1α/β in murine BPD and an involvement for MIP (macrophage inflammatory protein)-1α and TREM (triggering receptor expressed on myeloid cells)-1. Because it effectively shields newborn mice from BPD, IL-1Ra emerges as a promising treatment for a currently irremediable disease that may potentially brighten the prognosis of the tiny preterm patients. |
| Databáze: | OpenAIRE |
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