INFLUENCE OF HIGH VERSUS LOW INTESTINAL CONCENTRATION OF GRAM-NEGATIVE BACTERIA AND ENDOTOXIN ON THE SUSCEPTIBILITY OF MURINE MYELOPOIESIS IN BONE-MARROW AND SPLEEN TO CYTOSTATIC TREATMENT WITH ARA-C

The haematopoietic recovery after i.v. cytarabine was studied in C3H/Law mice as a measure for stem cell susceptibility in relation to the intestinal Gram-negative bacteria (GNB) and endotoxin. Reduction or elevation of GNB and endotoxin was induced by either polymyxin or bacitracin, both non-absorbable antibiotics. Bacitracin caused less suppression of the splenic cellularity after cytarabine, and an advancement of the recovery of femoral nucleated cells. The femoral recovery of CFU-GM exhibited a biphasic pattern. The speed and height of the rebound increase of CFU-GMs were significantly affected by the antibiotics. Thus, (modulation of) the murine intestinal microflora influences the haematopoietic recovery after cytostatic drugs. The mechanisms involved are complex; intestinal endotoxin seems to play a role.