RESUMEN
Tumour necrosis factor-alpha (TNF-alpha) is a monocyte (MO)-derived cytokine that plays an essential role in the immunological system. In the present study our aim was to evaluate the levels of TNF-alpha secreted by MO from cancer patients. Blood MO were obtained from 10 lung cancer patients (LCP), 10 colorectal cancer patients (CCP) and 10 healthy donors (HD). TNF-alpha levels in MO culture supernatants spontaneously (sp) secreted or after stimulation with LPS treatment were evaluated using a commercial ELISA kit (sensibility: 10-1000 pg/ml). Mean values, expressed as pg/ml were: LCP: sp= 452.6+/-107.2, LPS= 589.5+/-126.7); CCP: sp= 84.1+/-25.0, LPS= 437.3+/-93.2; HD: sp= 74.2+/-21.5, LPS= 573.5+/-87.1. We concluded that MO from LCP secrete high levels of TNF-alpha spontaneously (p< 0.003 versus HD) and it was also observed an absence of response to LPS treatment in the 33% of the cases in these patients.
Asunto(s)
Neoplasias Colorrectales/inmunología , Neoplasias Pulmonares/inmunología , Monocitos/inmunología , Factor de Necrosis Tumoral alfa/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Células Cultivadas , Neoplasias Colorrectales/sangre , Ensayo de Inmunoadsorción Enzimática , Humanos , Neoplasias Pulmonares/sangre , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
Monocytes (MO) from cancer patients present functional abnormalities, such as an altered secretion of soluble factors. In the present study, our aim was to evaluate the levels of interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and prostaglandin-E2 (PGE2) secreted in vitro by MO from lung cancer patients (LCP), spontaneously or after stimulation with lipopolysaccharide (LPS). Results showed that cytokine secretion was higher for MO from LCP than for MO from healthy controls, while in the 25% of the patients analysed, an absence of response to LPS treatment was found.
Asunto(s)
Citocinas/metabolismo , Dinoprostona/metabolismo , Neoplasias Pulmonares/metabolismo , Monocitos/metabolismo , Proteínas de Neoplasias/metabolismo , Estudios de Casos y Controles , Células Cultivadas , Humanos , Interleucina-1/metabolismo , Lipopolisacáridos/farmacología , Neoplasias Pulmonares/patología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
During the immune response, a great number of cytokines that modulate the function of mononuclear phagocytes are produced. Since interferons are one of the most important cytokines, the aim of this study was to evaluate the expression of HLA-DR antigen after an 18-h culture with human recombinant interferon-gamma (hrIFN-gamma) on freshly isolated peripheral blood monocytes from 16 colorectal cancer patients and 16 healthy donors, using an indirect immunofluorescence method. The results obtained showed that there was a decreased percentage of HLA-DR+ monocytes in the colorectal cancer patents (51 +/- 3%, p <0.01) compared with the healthy donors (77 +/- 2%). Treatment for 18 h with hrIFN-gamma increased the percentages of monocytes expressing HLA-DR: 71 +/- 3% for the cancer patients and 84 +/- 2% for the healthy donors (p <0.01 and <0.001, respectively). Our results demonstrate that after in vitro treatment with hrIFN-gamma, functionally altered monocytes from colorectal cancer patients can reach major histocompatibility complex II antigen expression values similar to those of healthy donors, thus improving the host's cellular immune response against the tumor.
Asunto(s)
Adenocarcinoma/inmunología , Antígenos de Neoplasias/biosíntesis , Neoplasias Colorrectales/inmunología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Antígenos HLA-DR/biosíntesis , Interferón gamma/farmacología , Leucocitos Mononucleares/inmunología , Adenocarcinoma/patología , Antígenos de Neoplasias/genética , Neoplasias Colorrectales/patología , Técnica del Anticuerpo Fluorescente Indirecta , Antígenos HLA-DR/genética , Humanos , Proteínas RecombinantesRESUMEN
The effect of cisplatin-containing chemotherapy regimen was evaluated on the expression of HLA-DR antigen in peripheral blood monocytes from patients with lung (LCP) and colorectal (CCP) cancer. Chemotherapeutic schedules employed in patients were etoposide and cisplatin for LCP and 5-fluorouracil and cisplatin for CCP. The results obtained showed a diminished percentage of monocytes expressing HLA-DR antigen in LCP (52.4 +/- 2.6, p < 0.004) and CCP (50.1 +/- 2.1, p < 0.001) respectively versus healthy donors (71.0 +/- 1.1%), and that their values increased during chemotherapy, raising them up to control level after the second cycle of treatment, independently of the course of the cancer growth. We conclude that both modalities of treatment allowed an increase of monocytes expressing HLA-DR antigen, suggesting that this effect may be due to cisplatin action.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/inmunología , Antígenos HLA-DR/sangre , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Monocitos/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Cisplatino/administración & dosificación , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/patología , Etopósido/administración & dosificación , Fluorouracilo/administración & dosificación , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
Bone marrow fibroblast colony-forming cells (CFU-F) were studied in fifteen consecutive untreated breast cancer patients (BCP) with clinical stages III and IV, and in sixteen normal controls (NC). A decreased number of CFU-F was observed in BCP compared to NC (p < 0.004). Confluence of the adherent cell layer was observed in all normal bone marrow mononuclear cells (MC) cultures, while a lower proportion of cultures from BCP (11/15) showed confluent adherent cell layers. When MC cultures of BCP were treated with indomethacin (Indo, 10(-6)M) 50% of them increased the number of CFU-F compared to the value obtained without treatment. In addition, a significant increase in the release of PGE2 in BCP cultures was observed before Indo treatment. Moreover, after MC were fractionated into adherent and non-adherent progenitors, the CFU-F decreased in both types of fractions of BCP compared to NC value (p < 0.02 and < 0.05, respectively). The number of light density MC per 10 ml of bone marrow aspirate and the number of trypsin-sensitive adherent progenitors were lower than NC in BCP (p < 0.02 and 0.013, respectively). Total MC and fibroblasts (fourth passage) were cultivated to evaluate the production of interleukin-1 beta (IL-1 beta) by ELISA methodology. Results indicated no difference of IL 1 beta spontaneous release when total MC cultures of both groups were compared. However, the levels of this cytokine were lower (< 10 pg/ml) in fibroblast culture supernatants of BCP compared to NC (1,217 +/- 74 pg/ml). Fibroblast cultures from BCP showed low or no release of IL-1 beta after muramyl-dipeptide (MDP. 1 microgram/ml) stimulation. In conclusion, the defective proliferative and confluence capacity of BCP fibroblastic progenitors may be related to the decrease in the production of IL-1 beta by these precursors.
Asunto(s)
Células de la Médula Ósea/patología , Neoplasias de la Mama/patología , Fibroblastos/patología , Biopsia con Aguja , Células de la Médula Ósea/metabolismo , Mama/citología , Neoplasias de la Mama/metabolismo , Células Cultivadas , Dinoprostona/biosíntesis , Dinoprostona/metabolismo , Femenino , Fibroblastos/metabolismo , Humanos , Interleucina-1/biosíntesis , Interleucina-1/metabolismo , Células Madre/patologíaRESUMEN
We studied the production of interleukin-1 (IL-1) by peripheral blood monocytes (Mo) from twelve normal subjects (NS) and eight and nine untreated lung and colorectal cancer patients (CP), respectively. No significant changes of extracellular IL-1 biological activity was observed between CP and NS by thymocyte proliferation assay. This result was independent that the cells were treated or not with lipopolisaccharide from E. coli (LPS, 10 micrograms/ml). Moreover, CP present normal amount of antigenic IL-1 beta in LPS treated Mo culture supernatants by enzyme-linked immunosorbent assay (ELISA). The biological activity of IL-1 released was not significant modified after indomethacin (Indo, 10(-6)M) and LPS + Indo treatments. Furthermore, patients showed a low percentage of LPS activated Mo with intracytoplasmatic IL-1 (alpha + beta) compared to normal values. These results were obtained by immuno-alkaline phosphatase staining using monoclonal antibody anti IL-1 (alpha + beta). In conclusion, CP had a reduced number of Mo with intracytoplasmatic IL-1 (alpha + beta) and the difference observed may depend on degradation or in the rate of synthesis of this cytokine.
Asunto(s)
Neoplasias Colorrectales/metabolismo , Interleucina-1/biosíntesis , Neoplasias Pulmonares/metabolismo , Monocitos/metabolismo , Animales , Neoplasias Colorrectales/patología , Espacio Extracelular , Humanos , Neoplasias Pulmonares/patología , RatonesRESUMEN
The expression of HLA-DR antigens and their capacity to reduce nitroblue tetrazolium (NBT) have been evaluated in monocytes (Mo) from 28 patients with colorectal carcinoma (CCa) before antineoplastic treatment as well as in 29 normal control (NC). Simultaneously, circulating immune complexes (CIC) levels were studied in both groups. The results were expressed as the media of percentages. They show a decrease of Mo bearing HLA-DR (p less than 0.001 vs NC) and increase of MO with capacity to reduce NBT (p less than 0.001 vs NC). An increase of CIC levels in CCa compared to the NC (p less than 0.001) was also observed. We can postulate that the decrease in HLA-DR expression could be caused by the increase of toxic oxygen intermediates whose production was induced by CIC or tumoral antigens adherence.