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.

Morphology of the bone marrow, spleen and liver during hematopoietic cell mobilization with cyclophosphamide in mice.

“…On day 4., we observed the reduction of spleen mass, what was in accordance with the discovery by Karp & Szczytkowski [35]. This effect can be related to severe leukopenia, with was deepest on day 4. after injection with CY, as reported by Shalit et al [34]. The increase of the amount of the cells between day 4. and 6. can be explained in two ways: the proliferation of cells in the spleen and the transfer of hematopoietic stem and pro- genitor cells from the bone marrow.…”

“…Moreover, in our observation CY produced temporary fibrosis of spleen deposits of reticulin were seen on the day 2., less visible on day 4. and the normal amounts were observed back on day 6. of the experiment. It was shown, that administration of CY was associated with marked cytopenia in the spleen [33] and directly induced a significant decrease in number of the myeloid progenitors [34]. On day 4., we observed the reduction of spleen mass, what was in accordance with the discovery by Karp & Szczytkowski [35].…”

Acacia ferrugineainhibits cyclophosphamide-induced immunosuppression and urotoxicity by modulating cytokines in mice

“…Several studies reported that IL-2, which plays a major role in maturation/development of lymphocytes and monocytes and stimulates natural killer (NK) cell secretion of IFN (Theze et al, 1996) -which in turn stimulates macrophage activation and T-cell differentiation (Borish & Rosenwasser, 1996), is impacted by CTX treatment (Guo et al, 2012). Similarly, GM-CSF, a hematopoietic growth factor pivotal for the regulation of bone marrow progenitor cell proliferation (Gasson, 1991), was also shown to be affected by CTX treatment (Shalit et al, 2001). Expectedly, here, CTX drastically reduced host serum levels of IL-2, IFN, and GM-CSF; these were significantly increased due to co-treatment with the extract.…”

Effect of Moxifloxacin on Production ofProinflammatory Cytokines from Human Peripheral BloodMononuclearCells

“…The immunomodulatory effects of antibiotics include alteration of phagocytosis, chemotaxis, endotoxin release, cytokine production, hematopoietic recovery after immunosuppression, and tumoricidal effects on certain cancer cells. Moreover some antibiotic agents can affect the life spans of cells through the induction or inhibition of apoptosis (6,(8)(9)(10)22).…”