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

Leuk Res. 1992 Oct;16(10):985-91. doi: 10.1016/0145-2126(92)90078-l.

Abstract

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.

MeSH terms

  • Animals
  • Bone Marrow / drug effects
  • Cecum / chemistry
  • Cytarabine / administration & dosage
  • Cytarabine / pharmacology*
  • Endotoxins / analysis*
  • Female
  • Gram-Negative Bacteria / isolation & purification*
  • Granulocyte-Macrophage Colony-Stimulating Factor / analysis
  • Hematopoietic Stem Cells / drug effects*
  • Injections, Intravenous
  • Intestines / microbiology*
  • Mice
  • Mice, Inbred C3H
  • Specific Pathogen-Free Organisms
  • Spleen / drug effects

Substances

  • Endotoxins
  • Cytarabine
  • Granulocyte-Macrophage Colony-Stimulating Factor