Influence of in vivo administration of GM-CSF and G-CSF on monocyte cytotoxicity.
The influence of colony-stimulating factors (CSFs) on the monocyte functions of 32 patients with refractory testicular cancer receiving high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) was tested. Eight patients were treated as a control group without CSF therapy, 12 patients received recombinant human granulocyte-macrophage-CSF (rhGM-CSF), and 12 patients received recombinant human granulocyte-CSF (rhG-CSF). For the assessment of monocyte activation induced by CSF expression of major histocompatibility complex (MHC) class I and II antigens, production of tumor necrosis factor (TNF) and monocyte-mediated cytotoxicity against tumor cell targets were chosen. Monocytes from patients with GM-CSF therapy showed a significant increase in MHC class I and II antigen expression as compared to patients without CSF treatment (p < 0.001). A significant increase in the expression of MHC class I was seen in monocytes from patients under G-CSF treatment, whereas no change of class II antigens was noticed. Production of TNF and monocyte-mediated cytotoxicity against U937 tumor cells was significantly increased in monocytes derived from patients receiving GM-CSF, as compared to those from the control group, while no effect was detectable in monocytes from patients with G-CSF therapy. However, after in vitro stimulation with interferon-gamma (IFN-gamma), monocytes derived from GM-CSF as well as from G-CSF treated patients responded with a significantly higher TNF-production and cytotoxicity than monocytes from control patients.
Wiltschke
C
C
Clinical Division of Oncology, University Hospital, Vienna, Austria.
Krainer
M
M
Wagner
A
A
Linkesch
W
W
Zielinski
C C
CC
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D013736:Testicular Neoplasms / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000628:therapy
D006680:HLA Antigens; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor