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Effects of r-metHuG-CSF on polymorphonuclear leucocyte kinetics and function in patients on continuous ambulatory
J Turzanski1, S P Crouch, M Andrews
1The David Evans Medical Research Centre, City Hospital NHS Trust, Nottingham.
Abstract:
End-stage renal failure (ESRF) patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are immunocompromised and exhibit abnormal circulating polymorphonuclear leucocyte (PMN) function, including reduced phagocytosis and intracellular killing. Six uraemic patients on CAPD were each given 300 microg granulocyte colony stimulating factor (G-CSF) every day for 5 d and PMN function tests were performed daily. By day 5 of the study CD11b expression was significantly decreased in response to N-formylmethionylleucylphenylalanine (fMLP) and opsonized Staphylococcus epidermidis stimulation, and expression of L-selectin (CD62L) was significantly decreased in response to opsonized Staphylococcus epidermidis stimulation. Further, superoxide anion production and Fc gammaRI (CD64) expression were found to be significantly increased and Fc gammaRII (CD16) expression was lowered. Circulating white cell and PMN counts were significantly elevated in response to treatment. Administration of G-CSF did not appear to have corrected the abnormalities in phagocytosis and intracellular killing. This study suggests that G-CSF does no harm to ESRF patients and influences uraemic PMN function in a manner that is comparable to its effects on PMN in non-uraemic subjects.
Insights
Granulocyte colony-stimulating factor (G-CSF) influences polymorphonuclear leucocyte (PMN) function in end-stage renal failure (ESRF) patients on dialysis. While G-CSF did not correct all PMN abnormalities, it appears safe for ESRF patients.
Area of Science:
- Nephrology
- Immunology
- Hematology
Background:
- End-stage renal failure (ESRF) patients on continuous ambulatory peritoneal dialysis (CAPD) are immunocompromised.
- These patients exhibit abnormal polymorphonuclear leucocyte (PMN) function, including reduced phagocytosis and intracellular killing.
- Understanding the impact of therapeutic interventions on PMN function in ESRF is crucial for patient management.
Purpose of the Study:
- To investigate the effects of granulocyte colony-stimulating factor (G-CSF) on PMN function in ESRF patients undergoing CAPD.
- To assess the safety and efficacy of G-CSF in modulating specific PMN functional parameters.
Main Methods:
- Six ESRF patients on CAPD received daily 300 microg G-CSF for 5 days.
- PMN function tests were conducted daily, including assessments of CD11b and L-selectin (CD62L) expression, superoxide anion production, and Fc gamma receptor (Fc gammaRI/CD64, Fc gammaRII/CD16) expression.
- Circulating white cell and PMN counts were monitored.
Main Results:
- G-CSF treatment led to a significant decrease in CD11b expression and L-selectin (CD62L) expression in response to stimulation.
- Superoxide anion production and Fc gammaRI (CD64) expression were significantly increased, while Fc gammaRII (CD16) expression was decreased.
- Circulating white cell and PMN counts were significantly elevated; however, phagocytosis and intracellular killing abnormalities were not corrected.
Conclusions:
- G-CSF influences uraemic PMN function in ESRF patients, with effects comparable to those observed in non-uraemic subjects.
- G-CSF administration did not appear to cause harm to ESRF patients.
- Further research is needed to fully elucidate the therapeutic potential of G-CSF in managing immune dysfunction in ESRF patients.