In vivo administration of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor increases neutrophil oxidative burst activity.
The influence of CSF therapy on the superoxide (O2-) releasing capacity in response to N-formyl-methionyl-leucyl-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Wiltschke
C
C
Clinical Division of Oncology, University Hospital, Vienna, Austria.
Krainer
M
M
Nanut
M
M
Wagner
A
A
Linkesch
W
W
Zielinski
C C
CC
D016026:Bone Marrow Transplantation; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism*; D016897:Respiratory Burst; D013481:Superoxides / Q000378:metabolism; D013736:Testicular Neoplasms / Q000378:metabolism* / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D016179:Granulocyte Colony-Stimulating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor