Acid aspiration-induced lung injury in rabbits is mediated by interleukin-8-dependent mechanisms.

HG Folkesson, MA Matthay, CA Hebert… - The Journal of …, 1995 - Am Soc Clin Investig
HG Folkesson, MA Matthay, CA Hebert, VC Broaddus
The Journal of clinical investigation, 1995Am Soc Clin Investig
Acid aspiration lung injury may be mediated primarily by neutrophils recruited to the lung by
acid-induced cytokines. We hypothesized that a major acid-induced cytokine was IL-8 and
that a neutralizing anti-rabbit-IL-8 monoclonal antibody (ARIL8. 2) would attenuate acid-
induced lung injury in rabbits. Hydrochloric acid (pH= 1.5 in 1/3 normal saline) or 1/3 normal
saline (4 ml/kg) was instilled into the lungs of ventilated, anesthetized rabbits. The rabbits
were studied for 6 or 24 h. In acid-instilled rabbits without the anti-IL-8 monoclonal antibody …
Acid aspiration lung injury may be mediated primarily by neutrophils recruited to the lung by acid-induced cytokines. We hypothesized that a major acid-induced cytokine was IL-8 and that a neutralizing anti-rabbit-IL-8 monoclonal antibody (ARIL8.2) would attenuate acid-induced lung injury in rabbits. Hydrochloric acid (pH = 1.5 in 1/3 normal saline) or 1/3 normal saline (4 ml/kg) was instilled into the lungs of ventilated, anesthetized rabbits. The rabbits were studied for 6 or 24 h. In acid-instilled rabbits without the anti-IL-8 monoclonal antibody, severe lung injury developed in the first 6 h; in the long-term experiments, all rabbits died with lung injury between 12 and 14 h. In acid-instilled rabbits given the anti-IL-8 monoclonal antibody (2 mg/kg, intravenously) either as pretreatment (5 min before the acid) or as treatment (1 h after the acid), acid-induced abnormalities in oxygenation and extravascular lung water were prevented and extravascular protein accumulation was reduced by 70%; in the long-term experiments, anti-IL-8 treatment similarly protected lung function throughout the 24-h period. The anti-IL-8 monoclonal antibody also significantly reduced air space neutrophil counts and IL-8 concentrations. This study establishes IL-8 as a critical cytokine for the development of acid-induced lung injury. Neutralization of IL-8 may provide the first useful therapy for this clinically important form of acute lung injury.
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The Journal of Clinical Investigation