Monocyte activation following systemic administration of granulocyte-macrophage colony-stimulating factor.
Twenty-four patients with solid malignancies were treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) on a Phase 1b trial. The objective of the study was to evaluate the effects of GM-CSF on peripheral blood monocyte activation. GM-CSF was administered by subcutaneous injection daily for 14 days. Immune parameters measured were monocyte cytotoxicity against the human colon carcinoma (HT29) cell line, serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and in vitro TNF-alpha and IL-1 beta induction. All patients were evaluable for toxicity. Fifteen patients were evaluable for immunologic response. Treatment with GM-CSF led to a statistically significant enhancement in direct monocyte cytotoxicity against HT29 cells. There was no increase in serum TNF-alpha or IL-1 beta and no consistent in vitro induction of TNF-alpha or IL-1 beta from monocytes posttreatment. Treatment was well tolerated overall. We conclude that treatment with GM-CSF can lead to enhanced monocyte cytotoxicity. Further studies are in progress to evaluate the effect of GM-CSF on other parameters of monocyte functions.
Kaplan Cancer Center, Division of Medical Oncology, New York University Medical Center, New York 10016.
A
A
Chachoua
R
R
Oratz
R
R
Hoogmoed
D
D
Caron
D
D
Peace
L
L
Liebes
R H
RH
Blum
J
J
Vilcek
D000328:Adult; D000368:Aged; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor