In vitro studies on the influence of doxorubicin in combination with recombinant interferon-gamma on human monocytes.
The maturation and differentiation process of human monocytes and human monocyte-derived macrophage cytotoxicity mediated by receptors for the Fc moiety of immunoglobulin G (Fc gamma Rs) were studied in vitro using the chemotherapeutic drug doxorubicin in combination with the biological response modifier (BRM) recombinant interferon-gamma (rIFN-gamma). Human monocytes were cultured for 9 days and treated with doxorubicin before, after, or on day 7 of the culture. rIFN-gamma was added continuously on day 0 or on day 7 of the culture, either alone or in combination with doxorubicin. In the presence of doxorubicin, all measured intracellular enzyme activities were at the same level as the controls and the rIFN-gamma treated cells. However, when monocytes were co-cultured for 9 days with rIFN-gamma alone or in combination with doxorubicin, enzyme levels decreased to between 45% and 61% of the controls. In control cultures ADCC activities against maximally sensitized hRBC mediated by Fc gamma RI and Fc gamma RII were 41.7 +/- 8.8% and 42.7 +/- 11.6%, respectively. When monocytes were exposed to rIFN-gamma continuously or 40 h before harvesting, Fc gamma RI ADCC activity increased to 78.9 +/- 9.8% and 68.1 +/- 8.1%, respectively, and Fc gamma RII ADCC activity to 56.3 +/- 8.4% and 55.4 +/- 7.3%, respectively. The addition of doxorubicin to monocyte cultures in the presence or absence of rIFN-gamma did not influence the lysis of the two types of sensitized hRBC. These observations indicate that doxorubicin does not negatively influence the activation state of monocytes/macrophages, induced by rIFN-gamma.
Van Schie
R C
RC
Division of Medical Oncology, University Hospital Nijmegen, The Netherlands.
De Mulder
P H
PH
Verstraten
H G
HG
Van Rennes
H
H
Wagener
D J
DJ
D000135:Acid Phosphatase / Q000032:analysis; D000920:Antibody-Dependent Cell Cytotoxicity; D000943:Antigens, Differentiation / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D002478:Cells, Cultured; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000494:pharmacology; D007521:Isocitrate Dehydrogenase / Q000032:analysis; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D011961:Receptors, Fc / Q000032:analysis; D017452:Receptors, IgG; D011994:Recombinant Proteins
D000943:Antigens, Differentiation; D011961:Receptors, Fc; D017452:Receptors, IgG; D011994:Recombinant Proteins; D004317:Doxorubicin; D007371:Interferon-gamma; D007521:Isocitrate Dehydrogenase; D000135:Acid Phosphatase