The role of inflammatory mediators in airway edema and obstruction produced in guinea pigs exposed to inhaled endotoxin or cotton dusts

Abstract

Endotoxin is present in significant quantities in several organic dusts [Dutkiewicz;1986;Lundholm et al., 1986] and is thought to play a role in some of the pulmonary effects of inhaled organic dusts, including cotton dust. Inhaled endotoxin and cotton dust are known to cause airway obstruction as well as peripheral lung injury.The purpose of the present study was to examine the effects of inhaled endo toxin on the conducting airways and to determine what role airway inflammation might play in the airway obstruction produced by endotoxin. Therefore, the effects of single and repeated exposures to endotoxin or cotton dust on airway edema, airway conductance, and the influx of inflammatory cells were examined in awake guinea pigs. Specific airway conductance (SGaw) was measured before and during exposure in awake, spontaneously breathing guinea pigs by the method of Agrawal [1981], and airway edema was measured by quantifying the extravasation of protein-bound Evans blue dye in the trachea and the mainstem and hilar bronchi. A single 3-hour exposure to 6.1 or 71.7 μg/m 3 endotoxin produced a dose-related decrease in SGaw by the end of exposure (22% and 34%, respectively). No significant decrease in SGaw was observed in control animals exposed to isotonic, pyrogen-free saline. The airway obstruction produced by inhaled endotoxin was accompanied by a dose-dependent increase in protein extravasation in the trachea, mainstem bronchi, and extrapulmonary hilar bronchi. Mean dye extravasation was increased by 106% and 314% in the mainstem bronchi, and by 124% and 247% in the hilar bronchi of animals exposed to the low and high doses of endotoxin, respectively. In the trachea, dye extravasation was significantly increased only in the high-dose endotoxin animals (136%). Expo sure to cotton dust (32 mg/m 3 ) with a comparable airborne endotoxin concentration (5.1 μg/m 3 ) produced a similar 43% decrease in SGaw. Airway edema was also observed after exposure to cotton dust. To study the hypothesis that airway edema may contribute to the airflow obstruction caused by inhaled endotoxin, animals were

Pulmonary Reactions to Organic Dust Exposures: Development of an Animal Model

“…As with cotton dust exposure, PMN recruitment into the airspaces was the most sensitive response to endotoxin inhalation, peaking at 1 jig/ml of endotoxin, while maximal breathing frequency occurred at 1000 pg/ml of endotoxin. The rapid breathing rate and PMN recruitment in response to endotoxin inhalation has also been reported by others (89)(90)(91) protein leakage (68), edema (93), and a decrease in airway conductance (68,93) in guinea pigs. Endotoxin exposure also induced the release of mediators such as TNFa (57,94) and PAF (95) in a manner similar to cotton dust exposure.…”