Effect of an LTB4 Aerosol Exposure on Pulmonary Function, Cell Populations, and Mediators in the Lungs of Rhesus Monkeys

Abstract

Six adult rhesus monkeys (5–7 kg) were anesthetized with sodium pentobarbital, 30 mg/kg iv, intubated, and exposed for 4 h, once per week, to air (baseline), normal saline, an inactive isomer of leukotriene B₄ (LTB₄), and LTB₄. Anesthesia was maintained with sodium pentobarbital, S mg/kg/h iv. Pulmonary function was monitored for a 30-min baseline period and during the 4-h exposure. After each exposure, the upper and lower airways were lavaged. The upper airway lavage was performed by inclining the animal head down, inserting a small catheter through the endotracheal (ET) tube to the carina, then instilling 15 ml normal 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. Two 10-ml aliquots of saline were instilled and gently suctioned via syringe. Cell counts and differentials were performed. Supernatant was analyzed for levels of LTB₄, LTC₄ and TxB₂. After the LTB₄ exposure, the animals were killed and the lungs were removed for histopathology. There were no significant changes in pulmonary function or cell populations from the upper airways after any treatment. LTB₄ levels were significantly increased over baseline only in the upper air-ways after the LTB₄ aerosol exposure. The lower airways showed a significant increase in total white cells due to a dramatic (1100%) increase in neutrophils after LTB₄ treatment only. The pulmonary tissue response was characterized by a multifocal accumulation of neutrophils in alveoli, neutrophilic infiltration of bronchiolar wall smooth muscle, and a slight accumulation of cell and mucous debris within small bronchi. It was concluded that, in these monkeys, an LTB₄ aerosol causes neutrophils to accumulate in the lungs without evidence of inflammation or altered pulmonary function.The LTB₄ and the 12-epi,6-trans-LTB₄ were synthesized and kindly supplied by D. R. Dobson and Dr. S. R. Baker, respectively, Eli Lilly and Company.