Lymphoma and Myeloma Cell Resistance to Cytotoxic Agents and Ionizing Radiations Is Not Affected by Exposure to Anti–IL-6 Antibody

Production of high levels of IL-6 is often correlated with resistance to cytotoxics or ionizing radiations, in cancer cell lines as in various cancer patients. We investigated whether monoclonal antibodies directed against IL-6 may enable to reverse resistance of cancer cell lines.We exposed ten haematological cancer cells from lymphoma, myeloma, or leukemia origins to cytotoxics or ionizing radiations and assessed the effects of anti–IL-6 antibody addition on cell proliferation, apoptosis, or IL-6 signaling. A strong correlation between IL-6 secretion, measured by ELISA, and resistance to doxorubicin as ionizing radiations was observed in the multiple myeloma U266 and the Burkitt's lymphoma Daudi and Namalwa cells. Although an anti–IL-6 antibody combined to both treatments efficiently blocked IL-6 signaling in U266 cells, expressing the IL-6 receptor gp80, it did not increase treatment-induced anti-proliferative and pro-apoptotic effects on these cells, as well as on Daudi and Namalwa cells. This lack of effect could be related to diverse factors: 1) a higher release of the soluble form of IL-6 receptor gp80 in response to doxorubicin and irradiation from all cell lines, 2) an impaired level of the IL-6 pathway inhibitor SOCS3 in Daudi cells, and 3) an increased release of IL-10 and TNFα, two cytokines involved in cell radio- and chemoresistance.These data support the fact that IL-6 is not the preponderant actor of cell resistance to cytotoxics and ionizing radiations, which seems to be regulated by a complex network of proteins