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Cytokines and cytokine network in silicosis and coal workers' pneumoconiosis
D Vanhée1, P Gosset, A Boitelle
1INSERM U 416, Institut Pasteur, Lille, France.
Abstract:
The alveolar macrophage (AM) is a critically important cell playing a prominent role in lung inflammation via the production of oxygen radicals, enzymes, arachidonic acid metabolites, and also a large panel of cytokines. Among interstitial lung disorders, silicosis and coal workers' pneumoconiosis (CWP) are the most widespread fibrotic lung diseases. Although their pathophysiology remains incompletely understood, several lines of evidence suggest the participation of cytokines produced by AMs at least in the initiation of the alveolitis. In vitro exposure of AMs (obtained from healthy subjects) to coal dust particles triggered a significant release of tumour necrosis factor (TNF) and interleukin-6, by comparison with titanium dioxide used as a biologically inert control dust. Moreover, it appeared that coal mine dust was more aggressive than similar concentrations of pure silica, suggesting that cytokine secretion induced by coal mine dust was not exclusively related to the presence of silica but resulted from a complex interaction between the different components. In silicosis and CWP, bronchoalveolar lavage showed a large influx of mononuclear phagocytes, with an increased spontaneous production of oxidants, fibronectin, neutrophil chemotactic factor, and also of interleukin-6 and TNF-alpha. This spontaneous cytokine release was associated with an increased cytokine messenger ribonucleic acid (mRNA) expression in the lungs of coal miners.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Alveolar macrophages (AMs) release inflammatory cytokines like TNF and IL-6 when exposed to coal dust. This highlights AMs' role in lung inflammation and fibrotic diseases such as silicosis and coal workers' pneumoconiosis (CWP).
Area of Science:
- Pulmonary immunology
- Occupational lung diseases
- Cellular inflammation
Background:
- Alveolar macrophages (AMs) are key players in lung inflammation, producing various mediators.
- Silicosis and coal workers' pneumoconiosis (CWP) are prevalent fibrotic lung diseases with incompletely understood pathophysiology.
- Cytokines produced by AMs are implicated in the initiation of alveolitis in these conditions.
Purpose of the Study:
- To investigate the role of AMs in lung inflammation induced by coal dust.
- To compare the inflammatory potential of coal mine dust and pure silica.
- To understand the cytokine release profile of AMs in response to occupational dust exposure.
Main Methods:
- In vitro exposure of AMs from healthy subjects to coal dust and titanium dioxide.
- Measurement of cytokine release (TNF, IL-6) and mRNA expression.
- Bronchoalveolar lavage analysis in patients with silicosis and CWP.
Main Results:
- Coal dust exposure significantly increased TNF and IL-6 release from AMs compared to inert titanium dioxide.
- Coal mine dust demonstrated greater inflammatory potential than pure silica, suggesting complex component interactions.
- Patients with silicosis and CWP showed increased mononuclear phagocyte influx and spontaneous production of oxidants and cytokines (IL-6, TNF-alpha).
Conclusions:
- AMs are crucial in initiating lung inflammation in response to coal dust exposure.
- The inflammatory response to coal mine dust involves multiple components beyond silica.
- Elevated cytokine production by AMs is a significant factor in the pathogenesis of silicosis and CWP.