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 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.
Shalit
I
I
Schneider Children's Medical Center of Israel and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Kletter
Y
Y
Halperin
D
D
Waldman
D
D
Vasserman
E
E
Nagler
A
A
Fabian
I
I
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
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