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 (O-2(-)) releasing capa city in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) of neutrophils from 32 patients with testicular cancer receiving high-dos e chemotherapy followed by autologous bone marrow transplantation (ABM T) 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 coll ected before initiation of chemotherapy and ABMT, during CSF administr ation on days 1 and 3 after leukocyte recovery, and 7 days after leuko cyte recovery (controls) or 3 days after the end of CSF therapy. Neutr ophils from patients who received GM-CSF showed a significantly higher superoxide anion release compared with control patients (p < 0.001). O-2(-) production in these patients was higher than that achieved by i n 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 simil ar but less pronounced increase was seen in patients who received G-CS F. In vitro preincubation of neutrophils from the same patients with G M-CSF, G-CSF, or TNF showed that O-2(-) production by neutrophils from patients receiving GM-CSF could not be further enhanced, whereas O-2( -) production by neutrophils derived from patients receiving G-CSF cou ld be further augmented by TNF but not by GM-CSF. Interestingly, neutr ophils from patients treated with GM-CSF but not those with G-CSF ther apy 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 O-2(- ) production.