RESUMO
Acredita-se que a produçäo abundante de fator de necrose tumoral alfa (TNFÓ) por macrófagos alveolares e outras células pode contribuir para o desenvolvimento de dano pulmonar permanente em muitas doenças inflamatórias. Há a necessidade de um agente, sem os efeitos colaterais dos corticosteróides, que possa reduzir a produçäo de TNFÓ pelos macrófagos ativados pela doença. Este estudo avaliou o efeito da talidomida na produçäo de TNFÓ induzida por lipopolissacarídeo (LPS) pelos macrófagos alveolares obtidos de pacientes com tuberculose e outras doenças associadas com a ativaçäo de macrófagos. Macrófagos alveolares obtidos de lavado broncoalveolar de 31 pacientes (tuberculose: 12, sarcoidose: 3, câncer do pulmäo: 5, bronquite crônica: 5, pneumonia: 6) forma estimulados com LPS isoladamente ou com LPS combinado ou com talidomida ou com dexemetasona. TNFÓ associado à célula, analisado por imunocitoquímica ou TNFÓ liberado por macrófagos, avaliado pelo método de ELISA, estavam muito aumentados nas células incubadas com LPS (p<0,05) e ambos estavam diminuidos após a adiçäo de talidomida (p<0,05) ou de dexametasona(p<0,05) atingindo níveis semelhantes aos observados quando os macrófagos eram incubados apenas com meio de cultura. Domesmo modo, a medida do mRNA do TNFÓ, medido pela hibridizaçäo in situ (ISH), aumentava após a incubaçäo com LPS (p<0,05) mas este aumento näo ocorria quando se adicionava talidomida (p<0,05) ou dexametasona (p<0,05). A capacidade da talidomida em reduzir a produçäo de TNFÓ induzida pelo LPS pelos macrófagos alveolares era a mesma tanto nas células de pacientes com tuberculose como dos pacientes com outras doenças. A capacidade da talidomida em reduzir a produçäo de TNFÓ por macrófagos alveolares destes pacientes com pneumopatias em atividade neste experimento sugere que ela, ou seus análogos, possam ter potencial medicamentoso em reduzir a produçäo de TNFÓ na doença clínica
Assuntos
Macrófagos Alveolares , Talidomida , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVE: Pulmonary fibrosis is a prominent feature of chronic lung disease of prematurity (CLD). We sought to determine the influence of the potent profibrotic cytokine transforming growth factor beta-1 (TGF-Beta 1) on the development of CLD. METHODS: We determined the concentration of active and total TGF-Beta 1 in bronchoalveolar lavage fluid obtained from 18 infants who subsequently had CLD (mean gestation, 25.7 weeks; birth weight, 816 gm) 15 (29.8 weeks, 1493 gm) who recovered from the respiratory distress syndrome, and 7 (35.1 weeks, 2441 gm) control infants. RESULTS: The concentration of both active and total TGF-Beta 1 was increased in the infants with CLD when compared with the respiratory distress syndrome and control groups. The increase in active and total TGF-Beta 1 was greatest on day 4 of age, when infants who eventually had CLD were compared with those who did not progress to CLD (active TGF-Beta 1, 39.5 vs 4.6 ng/ml; total TGF-Beta 1, 43.8 vs 13.8 ng/ml). In addition, immunocytochemistry studies localized pan-TGF-Beta to alveolar macrophages obtained by bronchoalveolar lavage. CONCLUSIONS: These observations indicate that TGF-Beta 1 may contribute to the fibrotic response that is observed in the lungs of infants who have CLD.
Assuntos
Líquido da Lavagem Broncoalveolar/química , Doenças do Prematuro/fisiopatologia , Pneumopatias/fisiopatologia , Fator de Crescimento Transformador beta/análise , Feminino , Humanos , Imuno-Histoquímica , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Síndrome do Desconforto Respiratório do Recém-Nascido/fisiopatologiaRESUMO
The origins of the high standardized mortality ratio (SMR) for coronary heart disease (CHD) among Indians in Britain, and the low SMR for West Indian immigrants, have been explored by a community survey in London. Serum lipoproteins, plasma glucose, haemostatic factors and other putative risk characteristics were measured in 75 Indian, 64 European and 24 West Indian men aged 45-54 years. These represented 81% of men registered with a general practice and resident within a defined area. In 51 men, diet was assessed by 5-day weighed inventory. Plasma phospholipid fatty acids (PFA) were measured in 18 Indians and 19 Europeans with dietary records. The relatively high HDL and HDL2-cholesterol concentrations, low LDL-cholesterol concentration, reduced fat intake, increased ratio of dietary polyunsaturated/saturated fat, relatively frequent use of alcohol, and lack of obesity in West Indians accorded with their low SMR from CHD. By contrast, only the relatively low HDL and HDL2-cholesterol concentrations, infrequency of alcohol consumption, and lower proportion of PFA as n-3 fatty acids of marine origin afforded explanations for the high SMR of Indians. Hyperglycaemia appeared similarly prevalent in Indians and West Indians, but less common in Europeans. Of the haemostatic factors, West Indians had a relatively low VIIc (not statistically significant), while Indians had an increased platelet count and reduced platelet volume. Improved understanding of these ethnic differences in CHD mortality may depend upon elucidation of the contrasts in HDL-cholesterol concentration.