EFFECT OF AN LTB(4) AEROSOL EXPOSURE ON PULMONARY-FUNCTION, CELL-POPULATIONS, AND MEDIATORS IN THE LUNGS OF RHESUS-MONKEYS

Six adult rhesus monkeys (5-7 kg) were anesthetized with sodium pentob arbital, 30 mg/kg iv, intubated, and exposed for 4 h, once per week, t o air (baseline), normal saline, an inactive isomer of leukotriene B-4 (LTB(4)), and LTB(4). Anesthesia was maintained with sodium pentobarb ital, 5 mg/kg/h iv. Pulmonary function was monitored for a 30-min base line period and during the 4-h exposure. After each exposure, the uppe r and lower airways were lavaged. The upper airway lavage was performe d by inclining the animal head down, inserting a small catheter throug h the endotracheal (ET) tube to the carina, then instilling 15 ml norm al saline through the catheter and collecting the fluid as it came out the ET tube. The lower airway lavage was performed with a fiberoptic bronchoscope placed at the level of generation 5-7 of a lower lobe. Tw o 10-ml aliquots of saline were instilled and gently suctioned via syr inge. Cell counts and differentials were performed. Supernatant was an alyzed for levels of LTB(4), LTC(4), and TxB(2). After the LTB(4) expo sure, the animals were killed and the lungs were removed for histopath ology. There were no significant changes in pulmonary function or cell populations from the upper airways after any treatment. LTB(4) levels were significantly increased over baseline only in the upper airways after the LTB(4) aerosol exposure. The lower airways showed a signific ant increase in total white cells due to a dramatic (1100%) increase i n neutrophils after LTB(4) treatment only. The pulmonary tissue respon se was characterized by a multifocal accumulation of neutrophils in al veoli, neutrophilic infiltration of bronchiolar wall smooth muscle, an d a slight accumulation of cell and mucous debris within small bronchi . It was concluded that, in these monkeys, an LTB(4) aerosol causes ne utrophils to accumulate in the lungs without evidence of inflammation or altered pulmonary function.