The role of pro- and anti-inflammatory responses in silica-induced lung fibrosis

• Main Authors: Lison Dominique, Leclercq Isabelle, Delos Monique, Arras Mohammed, Misson Pierre, Nihoul Aurélie, Barbarin Virginie, Huaux Francois
• Format: Article
• Language: English
• Published: BMC 2005-10-01
• Series: Respiratory Research
• Online Access: http://respiratory-research.com/content/6/1/112

<p>Abstract</p> <p>Background</p> <p>It has been generally well accepted that chronic inflammation is a necessary component of lung fibrosis but this concept has recently been challenged.</p> <p>Methods</p> <p>Using biochemical, histological, immunohistochemistry, and cellular analyses, we compared the lung responses (inflammation and fibrosis) to fibrogenic silica particles (2.5 and 25 mg/g lung) in Sprague-Dawley rats and NMRI mice.</p> <p>Results</p> <p>Rats treated with silica particles developed chronic and progressive inflammation accompanied by an overproduction of TNF-α as well as an intense lung fibrosis. Dexamethasone or pioglitazone limited the amplitude of the lung fibrotic reaction to silica in rats, supporting the paradigm that inflammation drives lung fibrosis.</p> <p>In striking contrast, in mice, silica induced only a limited and transient inflammation without TNF-α overproduction. However, mice developed lung fibrosis of a similar intensity than rats. The fibrotic response in mice was accompanied by a high expression of the anti-inflammatory and fibrotic cytokine IL-10 by silica-activated lung macrophages. In mice, IL-10 was induced only by fibrotic particles and significantly expressed in the lung of silica-sensitive but not silica-resistant strains of mice. Anti-inflammatory treatments did not control lung fibrosis in mice.</p> <p>Conclusion</p> <p>These results indicate that, beside chronic lung inflammation, a pronounced anti-inflammatory reaction may also contribute to the extension of silica-induced lung fibrosis and represents an alternative pathway leading to lung fibrosis.</p>