Am. J. Respir. Cell Mol. Biol., Volume 18, Number 1, January, 1998 51-59

Role of Interleukin-10 in the Lung Response to Silica in Mice

François Huaux, Jamila Louahed, Barry Hudspith, Clive Meredith, Monique Delos, Jean-Christophe Renauld, and Dominique Lison

Industrial Toxicology and Occupational Medicine Unit and Unit of Experimental Medicine, International Institute of Cellular and Molecular Pathology, Faculty of Medicine, Catholic University of Louvain, Belgium; Laboratory of Pathology, Hospital of Mont Godinne, Catholic University of Louvain, Louvain, Belgium; and Bibra International, Surrey, United Kingdom

There is evidence that, following exposure to crystalline silica, the release of several proinflammatory cytokines contributes to the induction of unbalanced inflammatory reaction leading to lung fibrosis. We have examined the potential contribution of interleukin-10 (IL-10), an anti-inflammatory cytokine, in the development of silicosis. In a mouse model of inflammatory lung reaction induced by intratracheal instillation of silica (0.5 mg and 5 mg DQ12/mouse), the levels of IL-10 protein (determined by ELISA) both in cells obtained after bronchoalveolar lavage (BAL) and in lung tissue homogenates were significantly increased when compared with controls. After in vitro lipopolysaccharide (LPS) stimulation (1 µg/ml), BAL cells obtained from silica-treated animals produced significantly more IL-10 protein and mRNA than cells obtained from control animals. To examine the role of IL-10 in the lung reaction induced by silica, IL-10- deficient animals were instilled with 5 mg of silica. Twenty-four hours after treatment, the amplitude of the inflammatory response (lactate dehydrogenase [LDH], protein and number of inflammatory cells in BAL) was significantly greater in IL-10-deficient animals than in the wild type. In contrast, the fibrotic response, evaluated by measuring lung hydroxyproline content and by histopathologic analysis 30 days after silica, was significantly less important in IL-10-deficient than in wild-type mice. Together, these data suggest that increased IL-10 synthesis induced by silica can limit the amplitude of the inflammatory reaction, but also contributes to amplify the lung fibrotic response.

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