Granulocyte colony-stimulating factor improves function of neutrophils from patients with acute liver failure.

OBJECTIVE: To evaluate the in vitro effects of granulocyte colony-stimulating factor (G-CSF) on function of neutrophils in acute liver failure (ALF). METHODS: Neutrophil functions (superoxide and hydrogen peroxide production; phagocytosis and killing; complement receptor expression) were determined simultaneously in 23 patients with ALF due to paracetamol overdose and compared with 23 healthy control subjects. RESULTS: Phagocytosis was reduced in neutrophils from ALF patients compared to controls (P< 0.005) and was significantly increased by incubation with 1,000 or 5,000 IU/ ml G-CSF (P< 0.05). This correlated with increased expression of CD11b (r= 0.93) and CD18 (r= 0.98) after incubation with 5,000 IU/ml G-CSF (P< 0.05). Killing was reduced in ALF neutrophils compared to controls (P< 0.005) and was similarly restored by G-CSF (P< 0.005). An increase in killing correlated with increases in production of superoxide (r = 0.96) and hydrogen peroxide (r= 0.97) by ALF neutrophils after incubation with 1,000 and 5,000 IU/ml of G-CSF when formylmethionylleucylphenylalanine (fMLP) was the stimulant. G-CSF at 5,000 IU/ml increased the production of hydrogen peroxide (P< 0.01) when zymosan was the stimulant. CONCLUSIONS: G-CSF improves the neutrophil dysfunction of ALF.