IL-8 IS ONE OF THE MAJOR CHEMOKINES PRODUCED BY MONKEY AIRWAY EPITHELIUM AFTER OZONE-INDUCED INJURY

A rhesus monkey interleukin (IL)-8 cDNA clone with >94% homology to th e human IL-8 gene was isolated by differential hybridization from a cD NA library of distal airways after ozone inhalation. In situ hybridiza tion and immunohistochemistry showed increased IL-8 mRNA and protein l evels in epithelial cells at 1 h but not at 24 h after inhalation of o zone. The appearance of IL-8 in airway epithelial cells correlated wel l with neutrophil influx into airway epithelia and lumens. Air-liquid interface cultures of tracheobronchial epithelial cells were exposed t o ozone in vitro. We observed a transient increase in IL-8 secretion i n culture medium immediately after ozone exposure and a dose-dependent increase in IL-8 secretion and mRNA production. In vitro neutrophil c hemotaxis showed a parallel dose and time profile to epithelial cell s ecretion of IL-8. Treatment with anti-IL-8 neutralizing antibody block ed >80% of the neutrophil chemotaxis in vitro. These results suggest t hat IL-8 is a key chemokine in acute ozone-induced airway inflammation in primates.