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.
Fukuda
A
A
First Department of Internal Medicine, Oska Medical College, Japan.
Kobayashi
H
H
Teramura
K
K
Yoshimoto
S
S
Ohsawa
N
N
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000328:Adult; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood*; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007700:Kinetics; D007958:Leukocyte Count; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects*; D011994:Recombinant Proteins
D000276:Adjuvants, Immunologic; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor