Ciprofloxacin inhibits human hematopoietic cell growth: synergism with tumor necrosis factor and interferon

Abstract

The cytokines tumor necrosis factor (TNF) and interferon (IFN) induce antiproliferative and cytotoxic activity in a variety of cell types. Ciprofloxacin (CFN)--a new fluoroquinolone antibiotic--has also been described, at high concentrations, to suppress hematopoietic cell growth and to affect cytokine production. This study examines the possible relationship between TNF alpha and IFN gamma, as components of host defense mechanisms, and CFN. To investigate the effect of CFN, either alone or combined with TNF or IFN, on normal human hematopoiesis, we examined in vitro changes in hematopoietic progenitor cell growth. We also studied the effect of CFN on human cytokine production by determining TNF, IFN, and colony-stimulating factor (CSF) production by human mononuclear leukocytes (MNC). Granulocyte and monocyte colony formation (granulocyte-macrophage colony-forming cells, GM-CFC) as well as erythroid burst formation (erythroid burst-forming units, BFU-E) were inhibited only by high nontherapeutic levels of CFN. Lower CFN concentrations, however, were inhibitory in the presence of low, noninhibitory concentrations of human recombinant (r)IFN gamma or rTNF alpha. CFN induced a striking dose-dependent increase in IFN gamma production and a decrease in CSF production by mitogen-stimulated MNC. No effect was observed, however, on TNF production by stimulated MNC. The synergistic inhibition of hematopoietic progenitor cell proliferation, achieved by combining low doses of CFN and of antiproliferative cytokines, may explain the occasional case of leukopenia or anemia observed in infected patients receiving CFN. This effect may also indicate the applicability of such a combination against malignant cell growth.