Effects of bacterial infection and irradiation on serum colony- stimulating factor levels in tolerant and nontolerant CF1 mice

Previous studies of germ-free and conventional irradiated mice led to the hypothesis that the increased levels of serum colony-stimulating factor (CSF) observed after whole-body irradiation (WBI) might be due to endotoxemia. Other investigations showed that CF1 mice preinjected with Salmonella typhosa endotoxin became tolerant or resistant to the CSF-elevating effect of endotoxin. In the current studies, tolerant CF1 mice were subjected to 1000 rads WBI; they developed serum CSF elevations comparable to those seen in control irradiated mice. Tolerance was not abolished by 1000 rads WBI or reversed by infection with gram-negative or gram-positive bacteria. Changes in inhibitor levels did not explain these results. These data indicated that serum CSF elevations observed after WBI may not be due solely to endotoxemia, despite the observation that limulus-reactive material, presumably endotoxin, was detected in 61.5% of CF1 mice 1-12 days after 1000 rads. In these studies, 29.4% of normal pooled plasma samples also were limulus positive, suggesting that transient endotoxemia may occur in some strains of normal mice. Infection of CF1 mice with gram-negative or gram-positive bacteria caused serum CSF elevations 6-24 hr after infection; levels returned to baseline by 48-144 hr in all groups. The return to normal in serum CSF levels in mice infected with gram-negative or gram-positive bacteria coincided with the development of tolerance to the CSF-elevating effect of endotoxin. Infected mice developed marked increases in marrow granulopoiesis and continued to show evidence of accelerated marrow granulocyte release 6-144 hr after infection.