RESUMEN
The effect of rubomycin and carminomycin on induction of suppressor cells in immunization of mice with high doses (2 . 10(9) cells) of sheep red blood cells (SRBC) or with the allogeneic spleen cells was studied. When the spleen cells of syngeneic animals hyperimmunized with SRBC were administered to intact cells, a marked specific suppression of both the antibody formation and the reaction of the delayed type hypersensitivity were observed. A decrease in the suppressor activity or its complete elimination as a result of exposure of the spleen cell donors to the antibiotics was indicative of a relatively selective effect of these drugs on the suppressor cells. This effect of the antibiotics increased after treatment of the spleen immune cells with the anti-T-serum and complement. However, the blocking effect of the antibiotics on the suppressor cells was not strictly specific, since they were detected in the syngeneic and allogenic systems with the cell transfer.
Asunto(s)
Reacciones Antígeno-Anticuerpo/efectos de los fármacos , Carubicina/inmunología , Daunorrubicina/análogos & derivados , Daunorrubicina/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Animales , Formación de Anticuerpos/efectos de los fármacos , Eritrocitos/inmunología , Inmunidad Celular/efectos de los fármacos , Inmunización , Masculino , Ratones , Ratones Endogámicos , Bazo/inmunología , Linfocitos T Reguladores/inmunología , Inmunología del Trasplante/efectos de los fármacosRESUMEN
The effect of doxorubicin, carminomycin and rubomycin on some immunological reactions was studied comparatively on mice. It was shown that doxorubicin had an immunodepressant effect on the synthesis of antibodies and antibody-forming cells. By the character of its immunodepressant effect doxorubicin was similar to rubomycin. In a dose of 0.3 of the LD50 doxorubicin had no effect on the transplantation immunity in the system of "transplant versus host" and did not prolong the lifetime of the skin graft.
Asunto(s)
Formación de Anticuerpos/efectos de los fármacos , Doxorrubicina/inmunología , Animales , Carubicina/inmunología , Daunorrubicina/inmunología , Eritrocitos/inmunología , Rechazo de Injerto/efectos de los fármacos , Reacción Injerto-Huésped/efectos de los fármacos , Hemaglutininas/análisis , Inmunización , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos CBA , Trasplante de Piel , Factores de Tiempo , Inmunología del Trasplante/efectos de los fármacosRESUMEN
The antitumor activity and effect on immunogenesis of rubomycin and carminomycin combinations with levamisole were studied comparatively. It was found that levamisole administered after carminomycin increased the intensity of delayed hypersensitivity in mice and only partially reduced immunoreactivity of the animals estimated by the number of antibody-forming cells in the spleen. No such effect was observed after injections of rubomycin. The antitumor effect of the combinations of the antibiotics wit levamisole was studied in experimental transplantable mouse lymphosarcoma L10-1. The use of rubomycin or carminomycin in combination with levamisole increased the survival of the animals and sometimes resulted in complete resolution of the tumors. No such effect was observed in treatment of the animals with the drugs alone. The data are indicative of a possible use of levamisole in combination with antitumor antibiotics in immunochemotherapy of tumors.
Asunto(s)
Carubicina/uso terapéutico , Daunorrubicina/análogos & derivados , Daunorrubicina/uso terapéutico , Levamisol/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Animales , Formación de Anticuerpos/efectos de los fármacos , Carubicina/inmunología , Daunorrubicina/inmunología , Relación Dosis-Respuesta Inmunológica , Combinación de Medicamentos , Evaluación Preclínica de Medicamentos , Hipersensibilidad a las Drogas/inmunología , Hipersensibilidad Tardía/inducido químicamente , Inmunidad Celular/efectos de los fármacos , Levamisol/inmunología , Masculino , Ratones , Ratones Endogámicos , Neoplasias Experimentales/tratamiento farmacológicoRESUMEN
The effect of rubomycin and carminomycin on the cellular immunity was studied on the model of delayed type hypersensitivity (DTH) in mice immunized with sheep red blood cells. It was shown that the antibiotics in the doses of 0.3-0.5 of the LD50 inhibiting the antibody formation induced intensive development of DTH. It was most pronounced on concurrent administration of the drugs or 24 hours after the immunization and did not depend on the antigen dose used for animal sensitization.
Asunto(s)
Carubicina/inmunología , Daunorrubicina/análogos & derivados , Daunorrubicina/inmunología , Eritrocitos/inmunología , Hipersensibilidad Tardía/inmunología , Animales , Formación de Anticuerpos/efectos de los fármacos , Inmunidad Celular/efectos de los fármacos , Inmunización , Masculino , Ratones , Ratones Endogámicos CBA , Ovinos/inmunología , Linfocitos T/efectos de los fármacosRESUMEN
The effect of carminomycin and rubomycin in equitoxic doses on the reaction of rejection of the allogenic skin graft and the reaction of the transplant to the host in mice (RTAH) was studied. Carminomycin significantly hampered the rejection of the skin graft and under certain conditions prevented development of the RTAH which indicated suppression of the formation of the clone of the immune T-killers. Rubomycin almost did not hamper the rejection of the skin graft and had no effect on the RTAH which indicated the absence of the selective effect on the system of K-killers. Carminomycin eliminated the RTAH only when it was administered to the recipients of the allogenic lymphoid cells 24 hours after implantation of the cells to the mice treated with cyclophosphamide. When carminomycin was administered to the donors of lymphoid cells 24 hours before the beginning of the experiment, it did not suppress the ability of the cells from these donors to induce the RTAH. Therefore, its effect was directed to the precursors of T-killers activated in the host of the allogenic recipient.
Asunto(s)
Carubicina/inmunología , Daunorrubicina/análogos & derivados , Daunorrubicina/inmunología , Tolerancia Inmunológica/efectos de los fármacos , Modelos Biológicos , Inmunología del Trasplante/efectos de los fármacos , Animales , Rechazo de Injerto/efectos de los fármacos , Reacción Injerto-Huésped/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Trasplante de Piel , Trasplante HomólogoRESUMEN
Sensitivity of the mice inoculated with ascitic NK/Ly cells and cured with carminomycin to repeated inoculation with the same tumour was studied. It was found that curing with carminomycin was accompanied by development of resistance to the repeated inoculation. Such resistance might be transferred to intact singeneic mice with a suspension of the cells of the spleen or lymph nodes from unsusceptible donors. The transfer of the thymus cells from the above donors protected the recipients only partially. The spleen cells from intact donors, as well as their lymph node cells did not inhibit the tumour development. The thymus cells of the intact mice induced some suppression, thus probably favouring the active immune response in the recipient. Curing of the NK/Ly-inoculated mice with carminomycin was a more effective method for induction of immunity to the tumour than immunization of mice with NK/Ly cells inactivated by UV irradiation in vitro
Asunto(s)
Carubicina/inmunología , Daunorrubicina/análogos & derivados , Linfoma/inmunología , Animales , Carubicina/uso terapéutico , Evaluación Preclínica de Medicamentos , Inmunidad/efectos de los fármacos , Inmunidad/efectos de la radiación , Inmunización , Inmunización Pasiva , Linfoma/tratamiento farmacológico , Masculino , Ratones , Ratones Endogámicos CBA , Trasplante de Neoplasias , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/inmunología , Rayos UltravioletaRESUMEN
Bovine serum albumin (BSA) and carminomycin, an anthracycline antibiotic, were subjected to conjugation with glutaraldehyde and their complexes with various contents of the antibiotic were prepared. The molar ratios of carminomycin and BSA were 8:1, 4:1, and 2:1. The antitumor effect of the preparations was studied on the models of mouse transplantable lymphosarcoma LIO equal 1 and ascitic forms of mouse lymphadenosis NK/Ly in vivo and in vitro. Their immunodepressant effect was evaluated from the decrease in the hemagglutinin titers in the mice immunized with sheep red blood cells. It was shown that when the toxicity of the complexes was the same, their antitumor and immunodepressant activities were different. The therapeutic activity of carminomycin in the four- and eight-substituted complexes was much higher than that of carminomycin alone. It is suggested that the differences in the activity of the complexes were connected with differences in their pharmacokinetics. It was found that the chemotherapeutic properties of the complexes may have changed by variation of the number of the cytostatic residues in the albumin molecule. The findings indicate that the whole complex molecule interacts with the malignant cell and not carminomycin preliminarily detached from it.
Asunto(s)
Antibióticos Antineoplásicos , Carubicina/uso terapéutico , Daunorrubicina/análogos & derivados , Albúmina Sérica Bovina/uso terapéutico , Animales , Formación de Anticuerpos/efectos de los fármacos , Carubicina/inmunología , Carubicina/toxicidad , Combinación de Medicamentos , Evaluación Preclínica de Medicamentos , Técnicas In Vitro , Dosificación Letal Mediana , Linfoma/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Ratones , Neoplasias Experimentales/tratamiento farmacológico , Albúmina Sérica Bovina/inmunología , Albúmina Sérica Bovina/toxicidad , Factores de TiempoRESUMEN
The dynamics of antibody genesis at various periods after single administrations of the antibiotics to mice and the mice spleen capacity to cooperate with intact T- and B- lymphocytes and macrophages in an immune response to sheep red cells were studied. It was found that rubomycin in equal with carminomycin doses by the toxicity induced more significant and slower reducing shifts in the immune response. Analysis of the cell mechanism of the immunosuppressive effects of rubomycin and carminomycin at early periods after their administration showed that the antibiotics inhibited mainly the functional activity of B-lymphocytes and had not effect on the helper function of T-lymphocytes. The immunological activity of macrophages was inhibited insignificantly.
Asunto(s)
Linfocitos B/efectos de los fármacos , Carubicina/inmunología , Daunorrubicina/análogos & derivados , Daunorrubicina/inmunología , Linfocitos T/efectos de los fármacos , Animales , Células Productoras de Anticuerpos/efectos de los fármacos , Células Productoras de Anticuerpos/inmunología , Linfocitos B/inmunología , Eritrocitos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos CBA , Ovinos , Bazo/inmunología , Linfocitos T/inmunologíaRESUMEN
The effect of carminomycin and rubomycin on the dynamics of the primary immune response to T-independent Vi-antigen of S. typhi was studied. Differences in the character of the antibiotic effect indicative of the high selective effect of carminomycin on the multiplying cells or precursors of the antibody forming plasmocytes were noted. It was found that the carminomycin inhibitory effect on synthesis of hemagglutinins to Vi-antigen was higher than that to sheep red blood cells. Carminomycin was shown to impair the formation of the immunological memory, while rubomycin did not suppress the development of the "memory cell" clone to T-independent antigen.
Asunto(s)
Reacciones Antígeno-Anticuerpo/efectos de los fármacos , Antígenos Bacterianos/inmunología , Antígenos de Superficie/inmunología , Carubicina/inmunología , Daunorrubicina/análogos & derivados , Daunorrubicina/inmunología , Salmonella typhi/inmunología , Animales , Memoria Inmunológica/efectos de los fármacos , Masculino , Ratones , Bazo/efectos de los fármacos , Linfocitos T/inmunología , Factores de TiempoRESUMEN
The dynamics of the titers and number of the antibody forming cells was studied within 26 hours after a single injection of anthracycline to immunized animals at various phases of the immune response. The specificity of the "rapid" effect of anthracyclines suggests that the low differentiated precursors of the antibody forming cells are the main target for the rubomycin effect and the immune competent cells in the state of multiplication and differentiation under the effect of the antigen are the main target for the carminomycin effect. The study was performed with noninbred mice immunized with sheep red cells.
Asunto(s)
Antibióticos Antineoplásicos/inmunología , Células Productoras de Anticuerpos/efectos de los fármacos , Naftalenos/inmunología , Animales , Antibióticos Antineoplásicos/administración & dosificación , Carubicina/inmunología , Recuento de Células , Daunorrubicina/inmunología , Glicósidos/administración & dosificación , Glicósidos/inmunología , Hemaglutininas/análisis , Inmunización , Terapia de Inmunosupresión , Técnicas In Vitro , Inyecciones Intravenosas , Masculino , Ratones , Naftalenos/administración & dosificación , Factores de TiempoRESUMEN
The immunodepressive effects of carminomycin and its 3 semi-synthetic derivatives, as well as rubomycin and its derivative R-103 were compared. It was found that 14-hydroxycarminomycin was much superior to the other substances in the experiments with synthesis induction suppression of antibodies against sheep red cells in mice. Suppression of the rejection of the skin allogenic grafts in the mice by carminomycin was higher as compared to that by the other substances. Probably different populations of the immune competent cells have selective sensitivity to separate anthracyclines.
Asunto(s)
Antibióticos Antineoplásicos/inmunología , Carubicina/inmunología , Daunorrubicina/análogos & derivados , Daunorrubicina/inmunología , Inmunosupresores , Animales , Formación de Anticuerpos/efectos de los fármacos , Carubicina/análogos & derivados , Relación Dosis-Respuesta Inmunológica , Inmunidad/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos CBA , Trasplante de Piel , Inmunología del Trasplante/efectos de los fármacos , Trasplante HomólogoRESUMEN
The effect of rubomycin and carminomycin on the dynamics of the primary and secondary immune response and formation of the immunologic memory to sheep red cells in mice was studied. Differences in the character of the antibiotics effect indicative of the higher selective action of carminomycin on multiplying cells, precursors of the antibody-forming plasmids, were found. Theoretically interesting discrepancies in the effect of the antibiotics on the content of the antibodies in the serum and the antibody-producing cells in the spleen were shown. It was demonstrated that carminomycin had no effect on formation of the immunologic memory inspite of a noticeable decrease in the total number of the spleen nuclear cells and the number of the antibody-forming cells at the moment of immunization under the effect of the antibiotic.
Asunto(s)
Antibióticos Antineoplásicos/inmunología , Formación de Anticuerpos/efectos de los fármacos , Carubicina/inmunología , Daunorrubicina/inmunología , Memoria Inmunológica/efectos de los fármacos , Animales , Células Productoras de Anticuerpos/efectos de los fármacos , Relación Dosis-Respuesta Inmunológica , Eritrocitos/inmunología , Inmunidad Celular/efectos de los fármacos , Masculino , Ratones , Ovinos , Factores de TiempoRESUMEN
The maximum immunodepressive effect of rubomycin and carminomycin was observed when the antibiotics were administered intravenously 24 hours after the immunization. The immune response induced by the sheep erythrocytes or the lipopolysaccharide was equally inhibited by rubomycin. Carminomycin in a dose of 0.5 mg/kg (0.1 of the LD50) to a larger extent inhibited the immune response stimulated by the lipopolysaccharide. Dependence of the immunodepressive effect of the antibiotics on their dose was found when the drugs were administered intravenously or orally.
Asunto(s)
Antibióticos Antineoplásicos/inmunología , Formación de Anticuerpos/efectos de los fármacos , Antígenos/administración & dosificación , Carubicina/inmunología , Daunorrubicina/inmunología , Animales , Células Productoras de Anticuerpos/efectos de los fármacos , Relación Dosis-Respuesta Inmunológica , Inmunización , Terapia de Inmunosupresión , Masculino , Ratones , Ratones Endogámicos CBARESUMEN
The morpho-functional state of the muscle lymphoid tissue of mice treated with karmionmycin (LD50, 1.1 mg/kg) was studied experimentally. Development of a number of changes evident of the cell disorganization in the lymphoid tissue was shown. The cytological shifts in the thymus and spleen were reversible, while the destructive period in the strumous gland was more prolonged. The morpho-structural normalization of the spleen did not coincide with reduction of its immunological function. The studies on the karminomycin effect on the kinetics of the primary immune response showed dependence of the antibiotic effect on the temporal ratio between the antigenic stimulus and the drug administration. The antibiotic had no effect on the inductive phase of the primary immune response but significantly suppressed its productive phase. On reproduction of the secondary immune response, a decrease in the content of the antibody-forming cells in the spleen was observed, production of the circulating antibodies remaining unchanged.