Effects of interferon-alpha on peripheral neutrophil counts and serum granulocyte colony-stimulating factor levels in chronic hepatitis C patients

Granulocytopenia is commonly observed in interferon-alpha (IFN-alpha) therapy. Granulocyte colony-stimulating factor (G-CSF) has been identified as a primary cytokine that regulates neutrophil production, but the kinetics of G-CSF in IFN-alpha-induced granulocytopenia remains unclear. We investigated the effects of IFN-alpha on serum G-CSF levels and peripheral neutrophil counts (NC) in 15 chronic hepatitis C patients treated with standard-dose (10 MU) recombinant IFN-alpha for 24 weeks by using a chemiluminescent enzyme immunoassay for G-CSF. The time course of change after a single IFN-alpha injection showed that mean serum G-CSF levels and NC increased significantly compared with pretreatment values (p < 0.05), and were statistically correlated (r = 0.914, p = 0.0015). On repeating IFN-alpha administration, this change gradually became unclear, and granulocytopenia occurred, accompanied by a significant increase in serum G-CSF (p < 0.01). Both values reached a plateau within 2 weeks after starting treatment, and recovered rapidly after the cessation of therapy. Although continuous administration of IFN-alpha caused a time-dependent granulocytopenia, our results suggest that a single injection of IFN-alpha would be a potent inducer of G-CSF and NC in vivo as a short-term effect and that there would be negative-feedback regulation between them during long-term IFN-alpha therapy.