Restoration of the acute phase response after infection in cyclophosphamide-treated mice by granulocyte...

The therapeutic effect of granulocyte colony-stimulating factor (G-CSF) against intramuscular infection with Pseudomonas aeruginosa in cyclophosphamide (CY)-treated mice was analyzed by measuring plasma levels of amyloid P-component (APC) and proinflammatory cytokine levels. CY (100 mg/kg) treatment of mice significantly suppressed plasma concentrations of APC and tumor-necrosis factor-alpha (TNF-alpha) following infection with P. aeruginosa, in associated with enhanced susceptibility of the treated mice to this bacterium. A 4-day treatment of CY-treated mice with recombinant human G-CSF (rhG-CSF) increased resistance of CY-treated mice, together with the marked restoration of APC and TNF-alpha productions. The capacity to produce interleukin 1-beta and TNF-alpha of peritoneal macrophages and also that to produce IL-6 of spleen cells were significantly enhanced by the in vivo administration of rhG-CSF in CY-treated mice. These results indicate that G-CSF may increase the functions of monocytes/macrophages directly or indirectly in vivo. Therefore, the therapeutic effect of rhG-CSF seems to consist of not only increases in the number and functions of neutrophils but also enhancement of monocyte/macrophage functions.