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Prevention of Oxygen-Induced Inflammatory Lung Injury by Caffeine in Neonatal Rats
Stefanie Endesfelder1, Evelyn Strauß1, Ivo Bendix2
1Department of Neonatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Insights
Caffeine treatment reduced lung inflammation and cell death in a rat model of bronchopulmonary dysplasia (BPD). This suggests caffeine may protect against oxygen-induced lung injury in preterm infants.
Area of Science:
- Neonatal Physiology
- Pulmonary Medicine
- Pharmacology
Background:
- Preterm birth is linked to respiratory issues like apnea and bronchopulmonary dysplasia (BPD).
- High oxygen therapy, while essential, can worsen BPD.
- Caffeine is used for apnea and shows potential in reducing BPD rates.
Purpose of the Study:
- To investigate caffeine's effects on inflammation and cell death in a hyperoxia-induced BPD model in newborn rats.
- To explore caffeine's impact on adenosine receptor expression in lung tissue.
Main Methods:
- Lung injury induced by 80% oxygen exposure in Wistar rats for 3 or 5 days.
- Caffeine (10 mg/kg) or PBS administered every two days from birth.
- Analysis of lung tissue at postnatal days 3, 5, and 15 using immunohistology, ELISA, and qPCR.
Main Results:
- Caffeine significantly reduced hyperoxia-induced cell death and apoptosis.
- Proinflammatory mediators and NFκB were decreased in caffeine-treated lungs.
- Caffeine modulated adenosine receptor transcription and increased immune cell infiltration.
Conclusions:
- Caffeine demonstrates antioxidative and anti-inflammatory properties in experimental oxygen-mediated lung injury.
- Findings support caffeine's therapeutic potential in mitigating BPD development mechanisms.
Background:
Preterm birth implies an array of respiratory diseases including apnea of prematurity and bronchopulmonary dysplasia (BPD). Caffeine has been introduced to treat apneas but also appears to reduce rates of BPD. Oxygen is essential when treating preterm infants with respiratory problems but high oxygen exposure aggravates BPD. This experimental study is aimed at investigating the action of caffeine on inflammatory response and cell death in pulmonary tissue in a hyperoxia-based model of BPD in the newborn rat. Material/Methods. Lung injury was induced by hyperoxic exposure with 80% oxygen for three (P3) or five (P5) postnatal days with or without recovery in ambient air until postnatal day 15 (P15). Newborn Wistar rats were treated with PBS or caffeine (10 mg/kg) every two days beginning at the day of birth. The effects of caffeine on hyperoxic-induced pulmonary inflammatory response were examined at P3 and P5 immediately after oxygen exposure or after recovery in ambient air (P15) by immunohistological staining and analysis of lung homogenates by ELISA and qPCR.
Results:
Treatment with caffeine significantly attenuated changes in hyperoxia-induced cell death and apoptosis-associated factors. There was a significant decrease in proinflammatory mediators and redox-sensitive transcription factor NFκB in the hyperoxia-exposed lung tissue of the caffeine-treated group compared to the nontreated group. Moreover, treatment with caffeine under hyperoxia modulated the transcription of the adenosine receptor (Adora)1. Caffeine induced pulmonary chemokine and cytokine transcription followed by immune cell infiltration of alveolar macrophages as well as increased adenosine receptor (Adora1, 2a, and 2b) expression.
Conclusions:
The present study investigating the impact of caffeine on the inflammatory response, pulmonary cell degeneration and modulation of adenosine receptor expression, provides further evidence that caffeine acts as an antioxidative and anti-inflammatory drug for experimental oxygen-mediated lung injury. Experimental studies may broaden the understanding of therapeutic use of caffeine in modulating detrimental mechanisms involved in BPD development.
