Acute hematologic effects of interferon alpha, interferon gamma, tumor necrosis factor alpha and interleukin 2.
This study was designed to investigate acute effects of various doses of the cytokines IFN-alpha, IFN-gamma, Interleukin 2 and tumor necrosis factor alpha on white blood cell differential counts. Before initiation of phase II trials, a dose-determination phase was performed, where three different dose levels of each cytokine were applied as a single dose. White blood cell differential counts were assessed immediately before and 2, 12, 24, 48 and 168 h after injection. Patients enrolled suffered from metastatic cancer or chronic active hepatitis. In addition, IFN-alpha was administered to five healthy volunteers. Results indicate that cytokines cause rapid and transient changes in the numbers of leukocyte subsets. Hematologic changes were cell-type- and cytokine-specific: transient lymphopenia was observed after administration of all four cytokines, reaching a nadir 12 to 24 h after subcutaneous injection. Administration of TNF-alpha and IFN-gamma also caused transient monocytopenia. Neutrophilia developed after administration of Interleukin 2, IFN-alpha and TNF-alpha. We conclude that cytokines play a key role in the regulation of peripheral blood cell traffic by their capacity to influence homing patterns of peripheral blood leukocytes.
Aulitzky
W E
WE
Department of Internal Medicine, University Hospital, Innsbruck, Austria.
Tilg
H
H
Vogel
W
W
Aulitzky
W
W
Berger
M
M
Gastl
G
G
Herold
M
M
Huber
C
C
D005260:Female; D006098:Granulocytes / Q000473:pathology; D006521:Hepatitis, Chronic / Q000473:pathology / Q000628:therapy; D006801:Humans; D007370:Interferon Type I / Q000009:adverse effects* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000009:adverse effects* / Q000627:therapeutic use; D007376:Interleukin-2 / Q000009:adverse effects* / Q000627:therapeutic use; D007700:Kinetics; D007958:Leukocyte Count; D007962:Leukocytes / Q000473:pathology*; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000473:pathology; D009369:Neoplasms / Q000473:pathology / Q000628:therapy; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects* / Q000627:therapeutic use
D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma