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Granulocyte-macrophage colony-stimulating factor may inhibit neutrophil migration in vivo
I E Addison1, B Johnson, S Devereux
1Department of Haematology, University College London, UK.
Abstract:
Recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) was administered by constant intravenous infusion to eight patients with malignant disease prior to chemotherapy. rh GM-CSF was given at a dose of 15 to 25 micrograms m-2 h-1 for 1 or 2 h. Neutrophil migration into an inflammatory zone was monitored throughout this period using a micropore skin window technique. Neutrophil migration into the micropore membrane prior to the commencement of the rh GM-CSF infusion was almost identical to that in eight normal control individuals (leading front distance of migrating neutrophils in 20-min period 81.3 +/- 7 microns in the patients compared to 79.4 +/- 4 microns in the control individuals). During the rh GM-CSF infusions there was a significant fall compared to controls in the number of neutrophils entering the membrane and the leading front distance (P less than 0.05). In four out of nine patient studies (eight patients) there was a greater than 30% fall from the pre-infusion level. In the control individuals the largest fall recorded was less than 10% and overall there was a progressive rise in the number of neutrophils entering the membrane throughout the period of study. This study suggests that intravenous infusion of rh GM-CSF may impair the ability of neutrophils to infiltrate an inflammatory focus.
Insights
Recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) intravenous infusion may impair neutrophil function. This study found rh GM-CSF reduced neutrophil migration into inflammatory sites in patients with malignant disease.
Area of Science:
- Immunology
- Hematology
- Pharmacology
Background:
- Recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) is used in patients with malignant disease.
- Neutrophils play a critical role in the immune response to inflammation and infection.
Purpose of the Study:
- To investigate the effect of rh GM-CSF intravenous infusion on neutrophil migration into an inflammatory focus.
- To compare neutrophil migration in patients receiving rh GM-CSF with normal control individuals.
Main Methods:
- Eight patients with malignant disease received rh GM-CSF intravenously prior to chemotherapy.
- Neutrophil migration was assessed using a micropore skin window technique.
- Migration was monitored during and after rh GM-CSF infusion and compared to controls.
Main Results:
- Neutrophil migration into the micropore membrane was similar in patients and controls before infusion.
- During rh GM-CSF infusion, a significant fall in neutrophil migration was observed compared to controls (P < 0.05).
- Four out of nine patient studies showed a >30% fall in neutrophil migration from pre-infusion levels.
Conclusions:
- Intravenous infusion of rh GM-CSF may impair neutrophil infiltration into inflammatory foci.
- Further research is needed to understand the clinical implications of this impaired neutrophil function.