Immunomodulatory effects of moxifloxacin in comparison to ciprofloxacin and G-CSF in a murine model of cyclophosphamide-induced leukopenia

We analyzed the effect of the two quinolones moxifloxacin and ciprofloxacin on the repopulation of hematopoietic organs and on the production of cytok ines by various organs of cyclophosphamide (CP)induced leukopenic mice. The effect was compared to that of G-CSF. Cyclophosphamide injection induced a severe leukopenia, with nadir at day 4 post-injection. All the quinolone a nd G-CSF-treated animals showed WBC > 500/muL at the nadir, compared to 50% of saline-treated mice. Cyclophosphamide induced a marked decrease in the number of myeloid progenitors (CFU-C) in bone marrow (BM) and spleen. Quino lone or G-CSF treatment resulted in a 1.4-4.3-fold increase in CFU-C number s in the BM; no enhancement was observed in the spleen. Treatment with CP r esulted in enhanced colony-stimulating activity (CSA) in bone shaft and spl een and decreased activity in bladder and lung. Treatment of CP-injected mi ce with quinolones significantly enhanced CSA in the bone shaft, spleen, lu ng and bladder on different days. In normal mice the highest levels of GM-CSF and IL-6 were observed in lung- conditioned medium (compared to bone shaft, spleen and bladder). Injection of CP resulted in a 22.5- and 93-fold decrease in GM-CSF and IL-6 levels, r espectively, in lung-conditioned medium, while treatment with quinolones re sulted in 2-4-fold increase in GM-CSF with no effect on IL-6 production. G- CSF treatment had no enhancing effect on GM-CSF nor on IL-6 production. We conclude that moxifloxacin and ciprofloxacin administered to CP-injected mi ce revert some of the immune suppressive effects of cyclophosphamide.