Acute inflammation and recovery in rats after intratracheal instillation of a 1 -> 3-beta-glucan (zymosan A)

Although endotoxin is a known potent stimulant of inflammatory responses, t he magnitude of pulmonary response following exposure to various organic du sts does not always correlate with endotoxin content of the dusts alone. Ot her components, such as 1 -->3 beta -glucans, derived from the inner cell w all of yeasts and fungi, have been implicated in organic dust toxic syndrom e. However, animal studies report conflicting results concerning the inflam matory potency of 1 -->3-beta -glucan. In this experiment, the pulmonary re action of rats to 1 -->3-beta -glucan (zymosan A) exposure was assessed. Ma le Sprague-Dawley rats were exposed via intratracheal instillation (IT) to zymosan A (dose range 0-5 mg/kg body weight). Rats were sacrificed 1-7 d po stexposure and the following pulmonary responses were monitored: (1) breath ing frequency, (2) differential cell counts of bronchoalveolar lavage (BAL) cells, (3) chemiluminescence (CL) as a measure of alveolar macrophage acti vation, (4) nitric oxide production by alveolar macrophages, (5) albumin le vels, and (6) lactate dehydrogenase (LDH) activity in the first acellular l avage fluid. Upon challenge with zymosan A, rats exhibited a dose-dependent pulmonary response at I d post IT that was significantly higher than the c ontrol level at a dose of 1-2.5 mg/kg body weight for each of these pulmona ry parameters. Post-IT enhancement of breathing frequencies and polymorphon uclear leukocytes (PMN) obtained by BAL both correlated very well with zymo san A concentration (r(2) = .95 and .99, respectively). Elevation of albumi n levels and LDH activity of the acellular BAL fluid also correlated (r(2) = .80) with the dose of zymosan. The recovery from a single intratracheal a dministration of zymosan A (2.5 mg/kg body weight) was monitored over 7 d. PMN and CL showed significant recovery from d 1 level by 3 d postexposure. Breathing frequencies and nitric oxide production showed significant recove ry from d I level by 4 d postexposure. A good correlation (r(2) = .8) betwe en recovery of PMN in BAL, CL, or nitric oxide production and the days post exposure was observed.