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- Abstract
- The cellular mechanism associated with the fibrotic process induced by inhaled mineral particles is currently thought to be due to repeated episodes of acute injury and inflammation leading to an excessive replication of mesenchymal cells and exuberant deposition of extracellular matrix proteins. Abundant literature has documented that silica-induced lung fibrosis can be orchestrated by pro-inflammatory mediators, in particular cytokines such as TNF- and IL-1. However the exact contribution of anti-inflammatory factors in the pathogenesis of lung fibrosis is still not fully delineated and remains a controversial topic in the literature. To evaluate the role of IL-10, a well characterized anti-inflammatory cytokine with important immunomodulatory properties, we examined the effect of overexpression of IL-10 gene during silica-induced pulmonary inflammation and fibrosis. Gene transfer was achieved by trans-oral injection of non-replicating adenovirus bearing the mouse IL-10 gene, either 24 hours before or 30 days after pulmonary administration of silica particles in C57BL/6 mice. The effect of AdIL-10 treatment on lung fibrosis was evaluated by measuring pulmonary hydroxyproline, soluble collagen and fibronectin contents 2 months after silica treatment. The results showed that silica induced-fibrosis assessed using all criteria was significantly increased in mice treated with AdIL-10 relative to those administrated with adequate control adenovirus (AdCTL) at both time points of adenoviral construct injection (day –1 and day 30). A more marked increase of recruited pulmonary lymphocytes associated with higher levels of IgG1 was also observed after AdIL-10 treatment in comparison to AdCTL situation, suggesting a polarization toward a type 2 immune response. These data showed that during mouse experimental silicosis IL-10 may possess pro-fibrotic function potentially via its activity on lymphocyte immune responses.
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