CYTOKINES AND CYTOKINE NETWORK IN SILICOSIS AND COAL-WORKERS PNEUMOCONIOSIS

The alveolar macrophage (AM) is a critically important cell playing a prominent role in lung inflammation via the production of oxygen radic als, enzymes, arachidonic acid metabolites, and also a large panel of cytokines, Among interstitial lung disorders, silicosis and coal worke rs' pneumoconiosis (CWP) are the most widespread fibrotic lung disease s, Although their pathophysiology remains incompletely understood, sev eral lines of evidence suggest the participation of cytokines produced by AMs at least in the initiation of the alveolitis, In vitro exposur e of AMs (obtained from healthy subjects) to coal dust particles trigg ered a significant release of tumour necrosis factor (TNF) and interle ukin-6, by comparison with titanium dioxide used as a biologically ine rt control dust. Moreover, it appeared that coal mine dust was more ag gressive than similar concentrations of pure silica, suggesting that c ytokine secretion induced by coal mine dust was not exclusively relate d to the presence of silica but resulted from a complex interaction be tween the different components, In silicosis and CWP, bronchoalveolar lavage showed a large influx of mononuclear phagocytes, with an increa sed spontaneous production of oxidants, fibronectin, neutrophil chemot actic factor, and also of interleukin-6 and TNF-alpha. This spontaneou s cytokine release was associated with an increased cytokine messenger ribonucleic acid (mRNA) expression in the lungs of coal miners. Two p rofibrotic factors, platelet-derived growth factor and insulin-like gr owth factor-1 (PDGF and IGF-1), were the factors mainly secreted by AM s in patients with progressive massive fibrosis, whereas transforming- growth factor-beta (TGF-beta) production was predominant in AMs obtain ed from patients with simple pneumoconiosis, suggesting a potential pr otective effect of TGF-beta on the development of pulmonary fibrosis i n coal workers' pneumoconiosis.