In Vivo Administration of Granulocyte-Macrophage Colony-Stimulating Factor and Granulocyte Colony-Stimulating Factor Increases Neutrophil Oxidative Burst Activity

Abstract

The influence of CSF therapy on the Superoxide (O₂ ^-) releasing capacity in response to N-formyl-methionylleucyl-phenylalanine (FMLP) of neutrophils from 32 patients with testicular cancer receiving high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) was assessed: 8 patients were treated as control group without CSF therapy, 12 patients received GM-CSF, and 12 patients received G-CSF. To monitor the kinetics of the respiratory burst, leukocytes were collected before initiation of chemotherapy and ABMT, during CSF administration on days 1 and 3 after leukocyte recovery, and 7 days after leukocyte recovery (controls) or 3 days after the end of CSF therapy. Neutrophils from patients who received GM-CSF showed a significantly higher Superoxide anion release compared with control patients (p < 0.001). O₂ ^- production in these patients was higher than that achieved by in vitro preincubation of neutrophils from control patients. Increased burst activity was seen only during infusion of GM-CSF and returned to pretherapeutic values after the end of GM-CSF administration. A similar but less pronounced increase was seen in patients who received G-CSF. In vitro preincubation of neutrophils from the same patients with GM-CSF, G-CSF, or TNF showed that O₂ ^- production by neutrophils from patients receiving GM-CSF could not be further enhanced, whereas O₂ ^- production by neutrophils derived from patients receiving G-CSF could be further augmented by TNF but not by GM-CSF. Interestingly, neutrophils from patients treated with GM-CSF but not those with G-CSF therapy retained a higher response to in vitro stimulation with GM-CSF or TNF after the end of CSF administration. These findings indicate that GM-CSF and G-CSF have different mechanisms of priming neutrophil O₂ ^- production.