The Effect of Intravenous Immunoglobulin (IVIG) on In vitro Activation of Circulating Neutrophils from CBA and C57BL/6 Mice with Fibrosarcoma S37

摘要

Background: The application of IVIG for cancer treatment is associated with the problem of variable patient’s response to IVIG, which might result from the peculiarities of neutrophil’s activation. Individual variations in the response to IVIG treatment can be elucidated by the comparison of CBA and C57BL/6 mouse strains. These two strains are considered as contrasting ones regarding function of their immune system. Here we studied zymosan-induced activation of circulating neutrophils from CBA and C57BL/6 mice developing fibrosarcoma. Results: The circulating neutrophils of CBA and C57BL/6 mice were studied at early stages of tumor growth. The WBC total and differential counting revealed the increase of neutrophil content in blood up to the day 7 after fibrosarcoma cells S37 inoculation. The neutrophils’ activity was measured as opsonized-stimulated (OZ) chemiluminiscent (CL) response of whole blood samples at various stages of tumor growth. At days 1 and 7 after inoculation the tumor-associated neutrophils priming was detected in both mouse strains. The effect was more prominent in C57BL/6 if measured in the presence of calcium. In addition to tumor associated priming, the IVIG-enhancing effect was registered at day 1 after inoculation of fibrosarcoma cells. As for normal neutrophils this effect was observed only in the presence of extracellular calcium. At day 7 after inoculation IVIG inhibited in vitro CL responses of blood samples stimulated with OZ (both of CBA and of C57BL/6). Conclusions: The activity of circulating neutrophils changes with the tumor development via the mechanisms, which depend on the strain type. These mechanisms are sensitive to IVIG and the effects of IVIG vary also with the stage of tumor growth. Developing fibrosarcoma induced priming of neutrophils in both mouse strains, mainly by calcium-dependent pathway. OZ-stimulated neutrophils from CBA were less active compared to C57BL/6, and implicated calcium-independent pathways even at day 7 of tumor development.