RESUMO
We have previously reported the antimetastatic effect of a single low-dose of cyclophosphamide (Cy) on L-TACB rat lymphoma. The phenomenon could be adoptively transferred in immunocompetent rats and is abolished in nude mice, facts for which an immunomodulatory explanation was proposed. The aim of this paper was to identify the mechanism(s) by which spleen cells from Cy-treated tumour-bearing rats could exert this antimetastatic activity. Conditioned media obtained by incubation of spleen cells from Cy-treated and non-treated tumour-bearing rats, under specific or non-specific stimulation, were assayed to evaluate their effect on lymphocyte proliferation. The production of transforming growth factor beta (TGF-beta), interleukin-10 (IL-10) and nitric oxide (NO) by conditioned media was also studied. The restoration of spleen lymphoproliferative responses to normal levels when exposed to media conditioned by splenocytes from Cy-treated tumour-bearing rats, together with a decreased production of suppressive cytokines TGF-beta, IL-10 and NO, suggest an enhancement of host antimetastatic immunity triggered by single low-dose Cy treatment.
Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Ciclofosfamida/administração & dosagem , Imunossupressores/administração & dosagem , Linfoma/prevenção & controle , Metástase Neoplásica/prevenção & controle , Animais , Divisão Celular , Feminino , Interleucina-10/análise , Linfoma/patologia , Masculino , Metástase Neoplásica/patologia , Nitritos/análise , Ratos , Fator de Crescimento Transformador alfa/análiseRESUMO
We have studied the effect upon the growth of a transplantable rat sarcoma, of an intraperitoneal inoculation of peritoneal exudate cell (PEC), spleen cells (SC) and non-adherent spleen cells (N-ASC) obtained from S. aureus previously inoculated rats and the same cells from normal rats (NPEC, NSC, NN-ASC). Inbred, adult rats were inoculated with 800 x 10(6) bacteria, killed by tyndalization. After 7 days, treated and normal animals were sacrificed and PEC, SC and N-ASC were obtained. Different groups of animals were inoculated with these cell populations. Simultaneously the rats received a s.c. inoculum of a transplantable sarcoma (S-E 100). Tumor size was measured on days 4, 7, 14, 21 and 28 after tumor challenge. A significant tumor growth inhibition was found with all three cell populations, but no effect was observed with normal cells. Tumor size on different days and tumor growth curves clearly demonstrate this effect. We conclude that Staphylococcus aureus inoculum as well as the cells from animals previously challenged with the bacteria induce tumor growth inhibition. The possibility that protein A of S. aureus may be involved in this phenomenon, or that the mechanism of tumor growth inhibition is mediated by an activation of different cell populations is discussed.
Assuntos
Sarcoma Experimental/imunologia , Staphylococcus aureus/imunologia , Animais , Ratos , Sarcoma Experimental/fisiopatologiaRESUMO
We have studied the effect upon the growth of a transplantable rat sarcoma, of an intraperitoneal inoculation of peritoneal exudate cell (PEC), spleen cells (SC) and non-adherent spleen cells (N-ASC) obtained from S. aureus previously inoculated rats and the same cells from normal rats (NPEC, NSC, NN-ASC). Inbred, adult rats were inoculated with 800 x 10(6) bacteria, killed by tyndalization. After 7 days, treated and normal animals were sacrificed and PEC, SC and N-ASC were obtained. Different groups of animals were inoculated with these cell populations. Simultaneously the rats received a s.c. inoculum of a transplantable sarcoma (S-E 100). Tumor size was measured on days 4, 7, 14, 21 and 28 after tumor challenge. A significant tumor growth inhibition was found with all three cell populations, but no effect was observed with normal cells. Tumor size on different days and tumor growth curves clearly demonstrate this effect. We conclude that Staphylococcus aureus inoculum as well as the cells from animals previously challenged with the bacteria induce tumor growth inhibition. The possibility that protein A of S. aureus may be involved in this phenomenon, or that the mechanism of tumor growth inhibition is mediated by an activation of different cell populations is discussed.
RESUMO
Se investigó el efecto modulador de la respuesta antitumoral de S. aureus y diversas poblaciones celulares en ratas portadoras de un sarcoma transplantable (S-E 100). Se comprobó en estas experiencias la capacidad inhibitoria del crecimiento del S-E 100 en ratas endocriadas, a través de la inoculación i.p. de células de exudado peritoneal (CEP), células de bazo (C.B.) y células de bazo no-adherenrtes (CBN-A), provenientes de ratas previamente desafiadas con S. aureus. También se inocularon i.p. células de animales normales (CEPN, CBN, CBN-AN). Se midió el tamaño del S-E 100 en los días 4, 7, 14, 21 y 28 después de iniciado el tratamiento. Se determinó que S. aureus, así como las poblaciones celulares provenientes de animales previamente inoculados con el germen (CE, CB, CBN-A), inhibe significativamente el crecimiento del tumor. Las células de animales normales no inciden en tal efecto. Se discute si este fenómeno es producido por la proteína A de S. aureus o a través de la activación de las poblaciones celulares (linfocitos, macrófagos, NK) inoculadas (AU)
Assuntos
Ratos , Animais , Sarcoma Experimental/imunologia , Staphylococcus aureus/imunologia , Sarcoma Experimental/fisiopatologiaRESUMO
Se investigó el efecto modulador de la respuesta antitumoral de S. aureus y diversas poblaciones celulares en ratas portadoras de un sarcoma transplantable (S-E 100). Se comprobó en estas experiencias la capacidad inhibitoria del crecimiento del S-E 100 en ratas endocriadas, a través de la inoculación i.p. de células de exudado peritoneal (CEP), células de bazo (C.B.) y células de bazo no-adherenrtes (CBN-A), provenientes de ratas previamente desafiadas con S. aureus. También se inocularon i.p. células de animales normales (CEPN, CBN, CBN-AN). Se midió el tamaño del S-E 100 en los días 4, 7, 14, 21 y 28 después de iniciado el tratamiento. Se determinó que S. aureus, así como las poblaciones celulares provenientes de animales previamente inoculados con el germen (CE, CB, CBN-A), inhibe significativamente el crecimiento del tumor. Las células de animales normales no inciden en tal efecto. Se discute si este fenómeno es producido por la proteína A de S. aureus o a través de la activación de las poblaciones celulares (linfocitos, macrófagos, NK) inoculadas
