肺胞マクロファージから産生されるInterleukin-1β,Tumor necrosis factor αの石綿肺病態における働きに関する研究

Abstract

Current cocepts of the pathogenesis of fibrotic changes in pulmonary asbestosis implies the roles of alveolar macrophages and cytokines produced by themselves. Tumor necrosis factor α(TNFα) and interleukin-1 β(IL-1β) are multifunctional cytokines produced by alveolar macrophages (AMs), cytokines which regulate inflammation and fibrosis. The aim of this study was to evaluate the role of TNFα and IL-1β secreted by AMs in the pathogenesis of pulmonary asbestosis. We isolated AMs by bronchoalveolar lavage from 11 subjects exposed to asbestos (AE) for a long time (32±8yrs) and from 7healthy controls (HC). AMs were stimulated with/without lipopolysaccharide (10μg/ml) for 24h and supernatants were assayed for TNFα and IL-1β by enzyme linked immunosorbent assay. AMs from AE produced higher levels of TNFα and 1L-1β upon stimulation with lipopolysaccharide than did the cells of HC. TNFα concentrations in BALFs were significantly higher in AE than in HC. IL-1β concentrations in BALFs were very low, and there was no significant difference between AE and HC. TNFα concentrations in BALFs and TNFα production from AMs positively correlated with the percentage of neutrophil in BALFs. AE were divided into two groups by roentogenographic profuound according to the ILO/UC classification (progressive group : more than 2, early group : less than Ⅰ). TNFα concentrations in BALFs were significantly higher in the progressive group than in the early group. In conclusion, these results indicate that TNFα is constitutively secreted by AMs from AE and is possibly associated with the pathogenesis of alveolitis and fibrosis due to asbestos exposure.