Modified endotoxin responses in rats pretreated with 1-->3-beta-glucan (zymosan A)

The present study investigates whether 1-->3-beta-glucans (zymosan particles) modify the pulmonary response of rats to endotoxin (lipopolysaccharide, LPS). Initial experiments were conducted to establish appropriate doses of LPS and regimens for exposure to zymosan and LPS. Interaction between zymosan and LPS exposures was determined to be the deviation from the sum of the individual effects of these agents. Treatment with zymosan on Day 1 and LPS on Day 2 modified several indices of pulmonary responsiveness, including tumor necrosis factor-alpha, albumin, and lactate dehydrogenase activity (LDH) in first acellular lavage fluid as well as the levels of chemiluminescence (CL), NO-dependent CL, and nitric oxide production in cultured lavaged alveolar macrophage cells determined 1 day after exposure. No significant deviation from additivity was found for breathing rate increase and polymorphonuclear leukocytes infiltration. Simultaneous administration of zymosan and LPS or administration of LPS before zymosan did not change these indices of pulmonary responsiveness. These data suggest that the inhibitory effect of 1-->3-beta-glucans on pulmonary responsiveness to endotoxin exposure was apparent only when rats were pretreated with 1-->3-beta-glucan. These results suggest that complex interaction of components may exist in exposure to organic dusts. Therefore, hazard may not be defined by measuring endotoxin or 1-->3-beta-glucans alone.