Production of tumor necrosis factor-alpha and interleukin-6 by human alveolar macrophages exposed in vitro to coal mine dust.

Following our previous demonstration of cytokine secretion by alveolar macrophages (AM) from coal miners and from patients with coal workers' pneumoconiosis, we investigated the effect of in vitro exposure to coal dust and to its silica content on tumor necrosis factor-alpha (TNF), interleukin (IL)-1-beta, and IL-6 production by normal human AM. TNF and IL-1-beta concentrations were estimated by a specific radioimmunoassay, while IL-6 levels were evaluated by the proliferation of 7TD1 cells. After 24-h culture, coal dust triggered a significant release of TNF and IL-6 at the dose of 0.1 mg/ml and more obviously at 1 mg/ml in comparison with titanium dioxide (TiO2), used as a biologically inert control dust (with 1 mg/ml of dust: 3,526 +/- 3,509 versus 330 +/- 138 pg TNF/ml and 224 +/- 74 versus 72 +/- 34 U IL-6/ml, respectively; P < 0.01 in both cases). After 3-h culture, a significant TNF secretion as well as an increased TNF mRNA expression were also detected for AM stimulated by coal dust at variance with TiO2. In contrast, no modification of IL-1-beta concentration could be evidenced in AM exposed to coal dust, although we detected an increased expression of specific mRNA expression. In order to define the role of silica among the main components of coal dust in AM activation, we evaluated the effect of silica (alpha-quartz, 30-mu-g/ml, which is the concentration and the type of silica present in our coal dust) alone or mixed with TiO2 (1 mg/ml) on monokine production. Both preparations had no effect on TNF, IL-1-beta, or IL-6 secretion by normal AM, whereas a higher dose of silica (0.1 mg/ml) induced a significant production of TNF (1,223 +/- 354 versus 315 +/- 158 pg/ml for AM exposed to TiO2; n = 3). In conclusion, we demonstrated that coal dusts induced the release of AM-derived mediators possibly involved in lung damage occurring in pneumoconiosis. However, this cytokine secretion was induced by compounds from our coal mine dust that are not directly related to the simple presence of silica, an additional argument supporting that besides silica other compounds or a complex interaction between the different particles exert a significant role in the development of coal workers' pneumoconiosis.