Abstract
Pulmonary lymphohistiocytic inflammation and fibrosis characterize bleomycin (BLM) lung injury. IL-12, a p70 cytokine produced primarily by macrophages and dendritic cells, promotes T-helper-1-mediated inflammation. IL-12 production by blood monocytes and bronchoalveolar large mononuclear cells (BAMC) was investigated at Days 1-14 following intratracheal administration of BLM. In the lung, BAMC showed a large peak of IL-12 expression at Day 5 that returned rapidly toward baseline. IL-12p40(-/-) mice treated with BLM intratracheally showed less pulmonary mononuclear cell inflammation at Day 7 than wild-type controls, whereas pulmonary fibrosis and hydroxyproline content were increased in IL-12p40(-/-) mice at Day 14. The expression of IP-10, RANTES, and eotaxin were decreased in IL-12p40(-/-) mice and lung IL-6 expression was increased, all compared to controls. We conclude that IL-12 promotes the lymphohistiocytic response to BLM and may inhibit the late development of pulmonary fibrosis.
Copyright 2002 Elsevier Science.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Anti-Bacterial Agents / pharmacology
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Bleomycin / pharmacology*
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Bronchoalveolar Lavage Fluid / cytology
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Chemokine CCL11
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Chemokine CCL5 / metabolism
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Chemokines, CC / metabolism
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Female
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Hydroxyproline / metabolism
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Interferon-gamma / metabolism
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Interleukin-10 / metabolism
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Interleukin-12 / genetics
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Interleukin-12 / immunology
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Interleukin-12 / metabolism*
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Interleukin-6 / metabolism
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Killer Cells, Natural / metabolism
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Leukocytes, Mononuclear / immunology
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Leukocytes, Mononuclear / metabolism
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Lung / drug effects*
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Lung / immunology
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Lung / metabolism
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Lung / pathology
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Macrophages, Alveolar / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Monocytes / metabolism
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Pneumonia / chemically induced
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Pneumonia / immunology*
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Pneumonia / physiopathology
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Pulmonary Fibrosis / chemically induced
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Pulmonary Fibrosis / immunology*
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Pulmonary Fibrosis / physiopathology
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Spleen / cytology
Substances
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Anti-Bacterial Agents
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Ccl11 protein, mouse
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Chemokine CCL11
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Chemokine CCL5
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Chemokines, CC
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Interleukin-6
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Bleomycin
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Interleukin-10
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Interleukin-12
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Interferon-gamma
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Hydroxyproline