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Previous issue date: 2014 === A Silicose ? uma pneumoconiose fibr?tica, irrevers?vel e potencialmente fatal, causada pela inala??o de poeira contendo s?lica cristalina. Causa disfun??o respirat?ria e desregula??o do sistema imunol?gico. Este trabalho foi dividido em dois estudos e teve como objetivos: avaliar as concentra??es plasm?ticas das citocinas e quimiocinas IL-1?, IL-6, IL-10, CCL2, CCL3, CCL11, CCL24, TNF-? e dos receptores sol?veis sTNFR1 e sTNFR2, de sujeitos expostos ? s?lica (SES), com e sem a silicose e de sujeitos n?o expostos ? poeira de s?lica; verificar se existe associa??o entre esses biomarcadores com a gravidade da silicose, avaliada pela radiografia de t?rax; verificar se existe associa??o entre os biomarcadores com o question?rio de qualidade de vida Saint George?s Respiratory Questionnaire (SGRQ), com o Teste de Caminhada de Seis Minutos (TC6), com a escala de dispneia do Medical Research Council e com a fun??o pulmonar, avaliada pelo volume expirat?rio for?ado no primeiro segundo (VEF1); verificar se existe associa??o entre os biomarcadores com o tempo de exposi??o ? s?lica; verificar se existe associa??o entre o tempo de exposi??o com a gravidade da silicose. M?todos: No primeiro momento do estudo, foram investigadas as concentra??es plasm?ticas de CCL2, CCL3, CCL11, CCL24, TNF-?, sTNFR1 e sTNFR2. Foram inclu?dos 57 SES, garimpeiros e lapid?rios de quartzo, sendo 36 com silicose. O grupo controle (GC) foi composto por 22 indiv?duos saud?veis sem hist?ria de exposi??o ? s?lica. Os biomarcadores foram avaliados por ELISA. Resultados: CCL3, CCL24, sTNFR1 e sTNFR2 estavam aumentados no grupo SES e nos SES com silicose em rela??o aos controles. As concentra??es plasm?ticas de sTNFR1 e sTNFR2 foram maiores nos SES, com e sem silicose. A concentra??o de sTNFR2 foi maior nos SES com silicose que nos SES sem silicose. Houve correla??o positiva entre sTNFR1 e sTNFR2 e a gravidade radiol?gica da silicose e o tempo de exposi??o. Al?m disso, sTNFR2 foi associado ? todas as categorias da gravidade radiol?gica. M?todos: No segundo momento do estudo foram investigadas as concentra??es plasm?ticas de IL-1?, IL-6, IL-10, TNF-?, sTNFR1 e sTNFR2, de 30 SES, sendo 23 indiv?duos silic?ticos e 7 sem silicose. O GC foi composto por 24 indiv?duos n?o expostos ? s?lica. Nessa fase foram tamb?m avaliados, a fun??o pulmonar, o grau de dispneia, a capacidade funcional e a qualidade de vida dos SES. Os biomarcadores foram avaliados por ELISA. Resultados: A concentra??o plasm?tica de IL-6 estava maior nos SES e nos pacientes com silicose comparados ao GC. Houve correla??o positiva entre a gravidade radiol?gica e o escore total do SGRQ, e correla??o negativa entre a gravidade radiol?gica e o VEF1. Foi encontrada correla??o negativa entre a concentra??o plasm?tica de sTNFR1 e a dist?ncia percorrida no TC6. IL-10 correlacionou-se negativamente com o escore total no SGRQ e correlacionou-se positivamente com a dist?ncia percorrida no TC6 e com o VEF1. Conclus?o: Os sujeitos expostos ? s?lica apresentaram aumento das concentra??es plasm?ticas de IL-6, CCL3, CCL24, sTNFR1 e sTNFR2. sTNFR2 foi associado ? gravidade radiol?gica e ? exposi??o precoce ? poeira de s?lica. A qualidade de vida relacionada ? respira??o foi afetada negativamente pela gravidade da silicose, que, por sua vez, prejudicou a fun??o pulmonar. Elevadas concentra??es plasm?ticas de sTNFR1 foram relacionadas com uma menor capacidade funcional. Al?m disso, a concentra??o elevada de IL-10, citocina anti-inflamat?ria, indicaram maior capacidade funcional, melhor fun??o pulmonar e qualidade de vida. Em conclus?o, este estudo mostrou que indiv?duos expostos ? poeira de s?lica apresentaram indica??o de inflama??o sist?mica, com preju?zo da fun??o pulmonar, da capacidade funcional e da qualidade de vida da popula??o avaliada. === ABSTRACT
Silicosis is a fibrotic, irreversible and potentially fatal pneumoconiosis caused by inhalation of dust containing crystalline silica. This disease is associated with respiratory dysfunction and dysregulation of the immune system. This research was divided into two studies and aimed to: evaluate the plasma levels of cytokines and chemokines IL-1?, IL-6, IL-10, CCL2, CCL3, CCL11, CCL24, TNF-? and soluble receptors sTNFR1 and sTNFR2 in subjects exposed to silica (SES), with and without silicosis and subjects unexposed to silica dust; to investigate the association between biomarkers with the silicosis severity, evaluated by chest X-rays; to check the association between biomarkers with Saint George's Respiratory Questionnaire (SGRQ), a quality of life questionnaire, with the Six-Minute Walk Test (6MWT), with the dyspnea scale of Medical Research Council and pulmonary function, as assessed by forced expired volume in one second (FEV1); to investigate the association between biomarkers with duration of exposure to silica; to investigate the association between duration of exposure and the radiological severity. Methods: In the first phase of the study, plasma levels of CCL2, CCL3, CCL11, CCL24, TNF-?, sTNFR1 and sTNFR2 were investigated. 57 SES, stone carving/polishing and/or quartz mining, 36 with silicosis were included. The control group (CG) consisted of 22 healthy men with no history of exposure. Inflammatory biomarkers were measured by ELISA. Results: CCL3, CCL24, sTNFR1 and sTNFR2 were greater in the SES group and in SES with silicosis than in the CG. Plasma levels of sTNFR1 and sTNFR2 were greater in SES, with and without silicosis. The concentration of sTNFR2 was greater in SES with silicosis than in SES without silicosis. There was a positive correlation between sTNFR1 and sTNFR2 and radiological severity of silicosis and duration of exposure. Moreover, sTNFR2 was associated with all categories of radiological severity. Methods: In the second phase of the study, plasma levels of IL-1?, IL-6, IL-10, TNF-?, sTNFR1 and sTNFR2 were investigated. There were 30 SES, 23 with silicosis and 7 subjects without silicosis. The CG was composed of 24 subjects unexposed to silica. In this phase we also evaluated pulmonary function, degree of dyspnea, functional capacity and quality of life of SES. Inflammatory biomarkers were measured by ELISA. Results: The plasma level of IL-6 was greater in SES and in patients with silicosis than in the CG. There was a positive correlation between radiological severity and SGRQ total score, whereas there was a negative correlation between radiological severity and FEV1. A negative correlation between plasma level of sTNFR1 and 6MWT was found. IL-10 was negatively correlated with the total score on the SGRQ and was positively correlated with the 6MWT and FEV1. Conclusion: The subjects exposed to silica showed increased plasma concentrations of IL-6, CCL3, CCL24, sTNFR1 and sTNFR2. sTNFR2 was associated with radiological severity and early exposure to silica dust. The respiration-related quality of life was negatively affected by the severity of silicosis, which, in turn, impaired lung function. Elevated plasma levels of sTNFR1 were associated with a lower functional capacity. In addition, high levels of IL-10, an anti-inflammatory cytokine, showed greater functional capacity, improved lung function and quality of life. In conclusion, this study showed that subjects exposed to silica dust had indicators of systemic inflammation with impaired pulmonary function, functional capacity, and quality of life of the studied population. === Disserta??o (Mestrado) ? Programa Multic?ntrico de P?s-gradua??o em Ci?ncias Fisiol?gicas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2014.
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