Role of interleukin-10 in the lung response to silica in mice.
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 microg/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.
Huaux
F
F
Industrial Toxicology and Occupational Medicine Unit, International Institute of Cellular and Molecular Pathology, Faculty of Medicine, Catholic University of Louvain, Belgium.
Louahed
J
J
Hudspith
B
B
Meredith
C
C
Delos
M
M
Renauld
J C
JC
Lison
D
D
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012822:Silicon Dioxide / Q000008:administration & dosage; D012829:Silicosis / Q000209:etiology* / Q000473:pathology; D014132:Trachea
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10; D012822:Silicon Dioxide; D007770:L-Lactate Dehydrogenase; D006909:Hydroxyproline