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.
Daenen
S
S
Department of Haematology, University of Groningen, The Netherlands.
Goris
H
H
de Boer
F
F
Halie
M R
MR
van der Waaij
D
D
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002432:Cecum / Q000737:chemistry; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology*; D004731:Endotoxins / Q000032:analysis*; D005260:Female; D006090:Gram-Negative Bacteria / Q000302:isolation & purification*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007275:Injections, Intravenous; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D008809:Mice, Inbred C3H; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000187:drug effects
D004731:Endotoxins; D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor