GM-CSF Augments the IL-4 Induced Cytotoxic Activity of Human Peripheral Blood Mononuclear Cells in the Presence of the Mouse Monoclonal Antibody 17–1A

The therapeutic effect of modulators of the immune system might be increased if administered in combination. Informations on their activity performed in different schedules may be obtained from in vitro analyses. In this study, human peripheral blood mononuclear cells (lymphocytes and monocytes) (PBMC) were treated simultaneously or sequentially with GM-CSF and IL-4, or vice versa, for different time periods. Cytokine activated PBMC were tested for cytolytic activity towards the human colorectal cell line SW11–16 in an 18 h antibody dependent cellular cytotoxicity (ADCC) assay using the specific MAM7–1A (mouse IgG2a). The simultaneous incubation of effector cells with both cytokines slightly increased the cytotoxicity induced by IL-4 or GM-CSF separately. Priming of PBMC with GM-CSF at the optimal concentration (10-3 µg/ml) for 1,2 and 4 h significantly enhanced the subsequent IL-4 induced activation of cytotoxicity. GM-CSF increased IL-4 induced cytotoxicity also at the suboptimal concentration (10-4 µg/ml), but to a lower extent. Priming of PBMC with IL-4 at optimal or suboptimal concentrations followed by stimulation with GM-CSF had no synergistic effect in ADCC. These results might have relevance as preliminary informations to exploit the concept of combining different biologic therapeutics for useful clinical protocols in cancer patients.