THE LEVEL OF SOME PRO- AND ANTI-INFLAMMATORY CYTOKINES IN MICE BEARING HIGHLY ANGIOGENIC LEWIS LUNG CARCINOMA AFTER APPLICATION OF CANCER VACCINES

Karaman O.M., Fedosova N.I., Voeykova I.M., Pyaskovska О.М., Didenko G.V., Solyanik G.I.

• R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine

Aim: To investigate the level of some pro- and anti-inflammatory cytokines in mice bearing highly angiogenic variants of Lewis lung carcinoma after the application of anticancer vaccines based on cell antigens of highly angiogenic (LLC/R9) or low-angiogenic (LLC) variants of the carcinoma. Object and me­thods: The study was performed on male C57/Bl mice bearing LLC/R9. As an adjuvant, a protein-containing metabolite of B. subtilis with m.m. of 70 kDa was used in cancer vaccine production (based on LLC or LLC/R9 cells). The vaccination schedule consisted of 4 subcutaneous injections that were started on day 12 after the LLC/R9 transplantation. Intact mice and unvaccinated mice bearing LLC/R9 were used as the control. On day 33 of tumor growth, the level of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin (IL) -1, -4, -10 were determined in blood serum (BS) and splenocytes supernatants. Results: IL-10 and IFN-γ play an important role in the development of tumor-associated anemia in mice bearing LLC/R9. The application of the vaccine based on LLC cells prevented the accumulation of IFN-γ in the BS at the late stages of tumor growth; this most likely underlies the possibility to gain antitumor protection, sufficient to reach antimetastatic effect. Nevertheless, this vaccine did not prevent the formation of an immunosuppressive state (increased ability of splenocytes to produce IL-10 with a simultaneous decrease in the production of IL-1β). The vaccine based on LLC/R9 cells, at the late stages of tumor growth, did not affect the BS level of IFN-γ and increased the level of IL-4 and IL-1β, which most probably caused the development of more severe anemia in this group. Moreover, this vaccine did not affect the functional state of splenocytes: a decrease in IFN-γ production was noted. Conclusion: the obtained results confirm the humoral (in particular, because of cytokines IL-10, IFN-γ and IL-1β level) mechanism of LLC/R9-assosiated anemia development; this can set the ground for the development of indications for auto­logous vaccines application according to paraneoplastic syndromes manifestations.