Neuropediatrics 2006; 210 - V58
DOI: 10.1055/s-2006-946340

Aerosolized interleukin antagonists: Potential role in the prevention of bronchopulmonary dysplasia?

M Chada 1, S Nögel 1, K von der Hardt 1, A Cubra 1, T Papadopoulos 2, W Rascher 1, M Kandler 1
  • 1Kinder und Jugendklinik
  • 2Institut für klinische Pathologie, Erlangen, D

Objective: In respiratory distress syndrome (RDS), interleukin-1 beta (IL-1 beta) and interleukin-8 (IL-8) are involved in the pulmonary inflammatory reaction and may play a key role in the development of bronchopulmonary dysplasia (BPD) in infants. Among inflammatory mediators IL-1 plays a role in the development of pulmonary hypertension. The purpose of this study was to determine whether pro-inflammatory pulmonary processes in surfactant depleted piglets can be successfully suppressed by systemic and aerosolized administration of an IL-1 receptor antagonist (IL-1Ra) and whether the administration of IL- 1Ra affects lung mechanics and pulmonary artery pressure.

Methods: Design: Experimental, prospective, randomized, observer-masked, controlled study.

Setting: Experimental laboratory at a university hospital.

Subjects: Eighteen anesthetized neonatal piglets assigned to three groups.

Interventions: After induction of lung injury by bronchoalveolar lavage, neonatal piglets

received repetitive treatment of either aerosolized IL-1Ra (IL-1Ra-Aerosol) or intravenous

IL-1Ra (IL-1Ra-i.v.), or saline solution as control.

Measurements and Main Results: Cardiopulmonary data were recorded for 12 hours. Gene expression of IL-1 beta and IL-8 in lung tissue was quantified by TaqMan real-time polymerase chain reaction (PCR). Lung injury score was calculated.

IL-1 beta and IL-8 mRNA expressions normalized to â-actin and hypoxanthine-guanine-phosphoribosyl transferase were significantly reduced in the IL-1Ra-Aerosol group but not in IL-1Ra-i.v. group compared to the control group.

IL-1Ra given as aerosol or intravenously significantly reduced mean pulmonary artery pressure (MPAP) and did not influence mean systemic arterial pressure (MAP) compared with the control group. The lung injury score were not significantly different between IL-1Ra groups and the control group.

Conclusion: Application of aerosolized IL-1Ra reduced early pro-inflammatory pulmonary reaction in this piglet model of surfactant depletion with pulmonary hypertension and might become a therapeutic option to reduce induction of lung fibrosis and the subsequent risk of BPD after lung injury. IL-1Ra significantly reduced MPAP without lowering MAP.