Stimulation of human committed bone marrow stem cells (CFU-GM) by chloramphenicol

Chloramphenicol, an antibiotic associated with reversible bone marrow suppression and fatal aplastic anemia, was found to increase human bone marrow granulocyte-macrophage colonies (CFU-GM) in vitro. Maximal stimulation was at a concentration of 1.0 micrograms/ml (3.1 microM), with inhibition at concentrations greater than 10 micrograms/ml. This effect was noted in normal donors and in children with neutropenia of various etiologies. Stimulation was ablated by depletion of bone-marrow-adherent cells and was restored by addition of peripheral-blood-adherent mononuclear cells. The stimulatory effect appears to be specific for chloramphenicol, as numerous structural analogues of chloramphenicol, including its three stereoisomers, did not show stimulation. The stimulation was present at plateau concentrations of colony-stimulating activity, suggesting that the stimulatory effect is not due to elaboration of excess colony-stimulating activity by chloramphenicol. We hypothesize that low concentrations of chloramphenicol stimulate CFU-GM by a highly specific interaction with adherent mononuclear cells and elaboration of an undefined growth factor.