Effect of Il-1 Blockade on Inflammatory Manifestations of Acute Ventilator-Induced Lung Injury in a Rabbit Model

Abstract

Ventilator-induced lung injury in children and adults is characterized by an initial inflammatory phase. To investigate whether the inflammatory cytokine, IL-I, plays a role in this process, a rabbit model of ventilator-induced injury was created. Animals maintained under pentobarbital anesthesia were primed for injury by undergoing lung lavage with 22 mL/kg of saline and then ventilated for 8 h with either F10₂ 0.21 and normal pressures or F10₂ 1.0 and high ventilator pressures. The animals exposed to hyperoxial/hyperventilation demonstrated a greater increase in lung lavage neutrophil counts and a higher histological injury score, as well as a faster decline in oxygenation compared to the control animals. A third group of rabbits 800 μg of recombinant IL-1 receptor antagonist after lung lavage and prior to the exposure to F10₂ 1.0 and high ventilator pressures. These animals had significantly lower concentrations of albumin and elastase and lower neutrophil counts in their lungs after the 8-h ventilatory period compared to hyperoxia/hyperventilation rabbits. IL-1 blockade had no effect on the decline in dynamic compliance and oxygenation seen in saline-treated hyperoxic/ hyperventilated rabbits. IL-1 is a mediator of acute inflammation due to ventilator-induced lung injury.