EFFECT OF IL-1 BLOCKADE ON INFLAMMATORY MANIFESTATIONS OF ACUTE VENTILATOR-INDUCED LUNG INJURY IN A RABBIT MODEL

Ventilator-induced lung injury in children and adults is characterized by an initial inflammatory phase. To investigate whether the inflammatory cytokine, IL-1, 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 F10(2) 0.21 and normal pressures or F10(2) 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 received 800 mu g of recombinant IL-1 receptor antagonist after lung lavage and prior to the exposure to F10(2) 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 hyperoxial/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.