1-->3-B-Glucans, derived from fungal cell walls, and endotoxin (LPS), derived from gram negative bacteria, are commonly found in organic dust. Both have been implicated in organic dust toxic syndrome. 1-->3-B-Glucans belong to a class of compound called Biological Response Modifiers. In a previous study, we demonstrated that intratracheal instillation (IT) of 1-->3-B-gIucans (zymosan A) caused a dosedependent inflammatory response in rats. The present study investigates whether 1-->3-B-gIucans modifies the pulmonary response of rats to endotoxin. Three experimental groups were investigated to evaluate the interaction of 1-->3-B-gIucans and endotoxin: Group A, IT-zymosan at day 1 and IT-LPS at day 2; Group B, ITLPS at day 1 and IT-zymosan at day 2; Group C, IT zymosan and LPS at day 1, IT PES at day 2. One day after these exposures, the following pulmonary response were monitored: (1) breathing frequency, (2) differential cell counts of bronchoalveolar lavage (BAL) cells, (3) chemiluminescence (CL) and (4) NO-dependent CL as a measure of alveolar macrophage activation, (5) nitric oxide production from alveolar macrophages, and (6) albumin and (7) lactate dehydrogenase (LDH) levels in the first acellular lavage fluid. Interaction between zymosan and endotoxin exposures was determined by the derivation from the sum of the individual effects of these agents. The results show that in group A (zymosan at day 1 before endotoxin at day 2) zymosan pretreatment decreased the subsequent pulmonary response to endotoxin. The other groups showed no significant difference between the results of combined exposure and the sum of the effects of endotoxin or zymosan exposure alone. These data suggest that the inhibitory effect of 1-->3-B-glucans on pulmonary responsiveness to endotoxin exposure is apparent only when rats were pre-treated with 1-->3-B-gIucan.
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California