Anakinra (IL-1R antagonist) lowers pulmonary artery pressure in a neonatal surfactant depleted piglet model.

In acute respiratory distress syndrome (ARDS) with pulmonary hypertension, interleukin-1 beta (IL-1 beta) and interleukin-8 (IL-8) are involved in the pulmonary inflammatory reaction. The purpose of this study was to determine whether systemic and aerosolized administered IL-1 receptor antagonist (IL-1Ra) Anakinra (Kineret) improves lung mechanics and pulmonary artery pressure in surfactant depleted newborn piglets. After induction of acute lung injury by lung 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. IL-1Ra given as aerosol or intravenously significantly reduced mean pulmonary artery pressure (MPAP) but did not influence mean systemic arterial pressure (MAP) compared with the control group. IL-1 beta and IL-8 mRNA expressions normalized to beta-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. The lung injury score was not significantly different between IL-1Ra groups and the control group. Application of aerosolized IL-1Ra reduced MPAP without affecting MAP in a piglet model of surfactant depletion with pulmonary hypertension. Furthermore, there is evidence for reduction of early pro-inflammatory pulmonary reaction. (c) 2008 Wiley-Liss, Inc.