Pulmonary overexpression of IL-10 augments lung fibrosis and Th2 responses induced by silica particles

V Barbarin, Z Xing, M Delos… - American Journal of …, 2005 - journals.physiology.org
V Barbarin, Z Xing, M Delos, D Lison, F Huaux
American Journal of Physiology-Lung Cellular and Molecular …, 2005journals.physiology.org
Chronic inflammation and proinflammatory cytokines as well as T helper type 2 (Th2)
cytokines have been involved in the pathogenesis of pulmonary injury and lung fibrosis. The
actual role of IL-10 in lung fibrosis is still unclear because this cytokine has been identified
as Th2 but possesses strong anti-inflammatory properties. To better dissect the potential role
of IL-10 in silica-induced lung fibrosis, IL-10 was overexpressed in the lung of mice by
adenoviral gene transfer during the inflammatory (administered at day− 1) or the fibrotic …
Chronic inflammation and proinflammatory cytokines as well as T helper type 2 (Th2) cytokines have been involved in the pathogenesis of pulmonary injury and lung fibrosis. The actual role of IL-10 in lung fibrosis is still unclear because this cytokine has been identified as Th2 but possesses strong anti-inflammatory properties. To better dissect the potential role of IL-10 in silica-induced lung fibrosis, IL-10 was overexpressed in the lung of mice by adenoviral gene transfer during the inflammatory (administered at day1) or the fibrotic (administered at day +30) stages of the disease. Pulmonary overexpression of IL-10 during both silica-induced lung inflammation and fibrosis exacerbated the fibrotic lesions as estimated by the measurement of hydroxyproline and other biochemical and histological markers. Increased expression of IL-10 significantly enhanced the number of lung lymphocytes and bronchoalveolar lavage fluid IgG1 but not IgG2a levels, indicating the induction of a Th2-like immune response. In addition, the production of the profibrotic Th2 cytokines IL-4 and IL-13 was also significantly increased upon IL-10 overexpression. No difference in transforming growth factor-β or PGE2 production was noted after adenoviral IL-10 treatment of silica-treated mice. Together, these data indicate that the increased expression of IL-10 significantly contributed to silica-induced lung fibrosis by exacerbating the Th2 response and the production of the profibrotic cytokines IL-4 and IL-13.
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