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[Use of in vitro methods in the immunotoxicologic evaluation of drugs]
The present paper proposes a model of in vitro tests examining the effect of drugs on the immunity system. The tests include the proliferation response of T cells (blastic transformation test of murine spleen cells and human peripheral mononuclear cells after stimulation by phytohaemagglutinin) and the antibody response (primary antibody response of murine spleen cells in the tissue culture after stimulation with sheep erythrocytes--demonstration of plaque-forming cells, formation of immunoglobulins by human peripheral mononuclear cells in the tissue culture after stimulation with pokeweed-mitogen--demonstration of immunoglobulins by ELISA test). Cytostatic agents derived from platinum were selected as the model group of drugs: cisplatin, oxoplatin and carboplatin in the concentrations ranging from 10(-4) to 10(-9) mol/l. In all tests IC50, i.e., the concentration of the drug producing 50% inhibition of response, was compared. The present authors have demonstrated that murine spleen nuclear cells are more sensitive to platinum cytostatics than human peripheral mononuclear cells; smaller concentrations of drugs are sufficient for 50% inhibition of immunity response of murine cells. Platinum cytostatics influence more the proliferative response of T cells than the antibody response. Platinum cytostatics act more on the cells in the stage of proliferation, or differentiation, i.e., after antigenic and mitogenic stimulation, than on the cells in a relative rest.
The present paper proposes a model of in vitro tests examining the effect of drugs on the immunity system. The tests include the proliferation response of T cells (blastic transformation test of murine spleen cells and human peripheral mononuclear cells after stimulation by phytohaemagglutinin) and the antibody response (primary antibody response of murine spleen cells in the tissue culture after stimulation with sheep erythrocytes--demonstration of plaque-forming cells, formation of immunoglobulins by human peripheral mononuclear cells in the tissue culture after stimulation with pokeweed-mitogen--demonstration of immunoglobulins by ELISA test). Cytostatic agents derived from platinum were selected as the model group of drugs: cisplatin, oxoplatin and carboplatin in the concentrations ranging from 10(-4) to 10(-9) mol/l. In all tests IC50, i.e., the concentration of the drug producing 50% inhibition of response, was compared. The present authors have demonstrated that murine spleen nuclear cells are more sensitive to platinum cytostatics than human peripheral mononuclear cells; smaller concentrations of drugs are sufficient for 50% inhibition of immunity response of murine cells. Platinum cytostatics influence more the proliferative response of T cells than the antibody response. Platinum cytostatics act more on the cells in the stage of proliferation, or differentiation, i.e., after antigenic and mitogenic stimulation, than on the cells in a relative rest.