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Intravenous immunoglobulins (IVIG) are used in the treatment of inflammatory, autoimmune conditions and cancer. However, the precise mechanism of their action and the mechanisms that underlie responsiveness and resistance of some patients to the IVIG therapy remain unknown. The anti-cancer effect of IVIg might be mediated by neutrophils, which regulate tumor development. We studied in vitro effects of IVIG on neutrophils from two immunologically contrasting mouse strains, CBA and C57BL/6. Results We examined total and differential WBC count, platelets count and the activity of normal neutrophils in intact CBA and C57BL/6 mice by method of luminol-dependent chemiluminescence (CL) of whole blood, and found significant difference in neutrophils, lymphocytes and platelets counts. Upon in vitro activation with opsonized zymozan (OZ), the C57BL/6 blood neutrophils showed no CL response at the absence of extracellular calcium while in the presence of calcium the CL responses of CBA and C57b blood were very similar. In the presence of IVIG, the calcium-dependent raise in OZ-activated CL response was registered only in C57BL/6 blood samples. Conclusions For the first time we demonstrate that IVIG cause the calcium-dependent neutrophils priming in vitro in whole blood of C57BL/6 but not in CBA mice.

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.

Background: The effect of IVIG in cancer treatment is likely to be mediated by immune cells that regulate tumor progression. Here we studied the effect of IVIG on tumor development in two immunologically contrasting mouse strains, CBA and C57BL/6. We compared the rate of tumor growth, the number of circulating neutrophils and oxidative characteristics of tumor tissue in IVIG-treated and control mice. Results: The animals were inoculated with fibrosarcoma S37 cells, and 14 days after inoculation there was a significant difference between IVIG-treated and control mice: IVIG treatment inhibited tumor growth in CBA mice and stimulated it in C57BL/6. The changes in tumor growth rate were associated with biochemical alterations in tumor tissue. According to the data of biochemical tests, IVIG-treatment influenced activity of tissue myeloperoxidase (neutrophil azurophilic granule enzyme) in CBA and C57BL/6 and of some antioxidant enzymes (glutathione-S-transferase, catalase, glutathione peroxidase) in C57BL/6 mice. Neutrophils content was increased in IVIG-treated CBA mice while in C57BL/6 it remained unaltered and significantly lower than in CBA as was shown by direct count on smears. Conclusions: These results suggest the tight link between the effects of IVIG upon neutrophils and tumor tissue redox balance as a part of regulatory mechanism of tumor growth.