title: Immunomodulatory effects of moxifloxacin in comparison to ciprofloxacin and G-CSF in a murine model of cyclophosphamide-induced leukopenia.
abstract: We analyzed the effect of the two quinolones moxifloxacin and ciprofloxacin on the repopulation of hematopoietic organs and on the production of cytokines 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 and G-CSF-treated animals showed WBC>500/microL 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. Quinolone or G-CSF treatment resulted in a 1.4-4.3-fold increase in CFU-C numbers in the BM; no enhancement was observed in the spleen. Treatment with CP resulted in enhanced colony-stimulating activity (CSA) in bone shaft and spleen and decreased activity in bladder and lung. Treatment of CP-injected mice with quinolones significantly enhanced CSA in the bone shaft, spleen, lung 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, respectively, in lung-conditioned medium, while treatment with quinolones resulted 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 mice revert some of the immune suppressive effects of cyclophosphamide.
authors: Schneider Children's Medical Center of Israel and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors: I
authors: I
authors: Shalit
authors: Y
authors: Y
authors: Kletter
authors: D
authors: D
authors: Halperin
authors: D
authors: D
authors: Waldman
authors: E
authors: E
authors: Vasserman
authors: A
authors: A
authors: Nagler
authors: I
authors: I
authors: Fabian
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001372:Aza Compounds; D001854:Bone Marrow Cells; D001842:Bone and Bones / Q000378:metabolism; D002452:Cell Count; D002939:Ciprofloxacin / Q000494:pharmacology*; D017077:Culture Media, Conditioned; D046508:Culture Techniques; D003520:Cyclophosphamide; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D024841:Fluoroquinolones; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006098:Granulocytes; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D015850:Interleukin-6 / Q000096:biosynthesis; D007958:Leukocyte Count; D007970:Leukopenia / Q000139:chemically induced*; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000077266:Moxifloxacin; D011804:Quinolines; D015363:Quinolones / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D017077:Culture Media, Conditioned; D016207:Cytokines; D024841:Fluoroquinolones; D015850:Interleukin-6; D011804:Quinolines; D015363:Quinolones; D016179:Granulocyte Colony-Stimulating Factor; D002939:Ciprofloxacin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D000077266:Moxifloxacin