Interleukin-9 reduces lung fibrosis and type 2 immune polarization induced by silica particles in a murine model

American Thoracic Society 2001

We examined the effect of interleukin (IL)-9, a cytokine active on B and T lymphocytes and associated with bronchial asthma, on the development of lung fibrosis induced by crystalline silica particles. Therefore, we compared the response to silica (1 and 5 mg/animal, intratracheally) in transgenic mice that constitutively express high levels of IL-9 (Tg5) and their wild-type counterparts (FVB). At 2 and 4 mo after treatment with silica, histologic examination and measurement of lung hydroxyproline content showed that the severity of fibrosis was significantly less important in Tg5 mice than in their wild-type counterparts. Intraperitoneal injection of IL-9 in C57BL/6 mice also reduced the amplitude of silica-induced lung fibrosis. The reduction of lung fibrosis by IL-9 was associated with a significant expansion of the B-lymphocyte population, both in bronchoalveolar lavage (BAL) and in the pulmonary parenchyma. In wild-type animals, silica-induced fibrosis correlated with markers of a T helper 2-like response such as upregulation of IL-4 levels in lung tissue and an increased immunoglobulin (Ig) G1/IgG2a ratio in BAL. Immunohistochemical studies demonstrated that the upregulation of IL-4 associated with the development of fibrosis was mainly localized in inflammatory alveolar macrophages. In transgenic mice, the level of IL-4 in lung homogenates was not significantly affected by silica treatment, and a reduced IgG1/IgG2a ratio was observed upon treatment with silica. The levels of interferon-gamma were significantly decreased after silica treatment in both strains. Together, these observations point to an antifibrotic effect of IL-9 in pulmonary fibrosis associated with a limitation of the type 2 polarization which accompanies lung fibrosis.

Animals; Bronchoalveolar Lavage Fluid; Crystallization; Disease Models, Animal; Flow Cytometry; Gene Expression; Hydroxyproline; Immunoglobulin G; Interferon Type II; Interleukin-4; Interleukin-9; Lung; Macrophages, Alveolar; Mice; Mice, Inbred C57BL; Mice, Transgenic; Pulmonary Fibrosis; Recombinant Proteins; Silicon Dioxide; Th1 Cells; Th2 Cells; info:eu-repo/semantics/article

Open access content. Open access content
info:eu-repo/semantics/restrictedAccess

English

UCDLC oai:dial.uclouvain.be:boreal:8810
boreal:8810
info:doi/10.1165/ajrcmb.24.4.4249
info:pmid/11306428
urn:ISSN:1044-1549
urn:EISSN:1535-4989
1130585924

UNIVERSITE CATHOLIQUE DE LOUVAIN
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