Effects of interleukin-6 on mobilization of primitive haemopoietic cells into the circulation.
Twenty-seven patients with advanced adenocarcinoma were studied. Groups of three patients received interleukin-6 (IL-6) in doses ranging from 0.5 to 20 micrograms/kg by daily subcutaneous injection on days 1-7 and 22-49. Four patients received IL-6 2.5 micrograms/kg/d with GM-CSF 5 micrograms/kg/d and three patients received IL-6 2.5 micrograms/kg/d with IL-3 5 micrograms/kg/d. Circulating platelet numbers increased 1.65-fold during IL-6 treatment, in a dose-dependent fashion (P = 0.01). This increase is inferior to that expected from laboratory studies. No significant change in total WBC was seen after IL-6 alone. After treatment with IL-6, significant increases in numbers of circulating mononuclear cells (2.2-fold, P = 0.006) and GM-CFC numbers (3.2-fold, P = 0.01) were seen, but there were no changes in circulating megakaryocyte-CFC numbers. In contrast, after treatment with IL-6 and GM-CSF, larger increases in both circulating GM-CFC (20-fold, P = 0.04) and megakaryocyte-CFC numbers (18-fold, P = 0.03) were seen. Increases in blood progenitors after treatment with IL-6 and IL-3 did not achieve statistical significance. The ability of peripheral blood mononuclear cells to generate and sustain long-term haemopoiesis in vitro was similar in IL-6-treated patients to that in untreated control subjects. No significant changes in the incidence of bone marrow progenitors or their cycling status (assessed by thymidine suicide) were seen. These data suggest that IL-6 alone will not be clinically useful to mobilize blood progenitor cells in cancer patients.
Pettengell
R
R
CRC Department of Medical Oncology, Christie Hospital, Manchester.
Luft
T
T
de Wynter
E
E
Coutinho
L
L
Young
R
R
Fitzsimmons
L
L
Scarffe
J H
JH
Testa
N G
NG
D000230:Adenocarcinoma / Q000097:blood* / Q000188:drug therapy; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000502:physiology; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy; D004338:Drug Combinations; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000097:blood / Q000188:drug therapy; D010190:Pancreatic Neoplasms / Q000097:blood / Q000188:drug therapy; D014410:Tumor Stem Cell Assay
D004338:Drug Combinations; D007377:Interleukin-3; D015850:Interleukin-6; D016178:Granulocyte-Macrophage Colony-Stimulating Factor