Respiratory Reovirus 1/L Induction of Diffuse Alveolar Damage: Pulmonary Fibrosis Is Not Modulated by Corticosteroids in Acute Respiratory Distress Syndrome in Mice |
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Authors: | Lucille London Elizabeth I Majeski Sanja Altman-Hamamdzic Candace Enockson Manjeet K Paintlia Russell A Harley Steven D London |
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Institution: | Department of Microbiology and Immunology, Medical University of South Carolina, PO Box 250504, 173 Ashley Avenue, Charleston, South Carolina;Department of Pathology and Laboratory Medicine, Medical University of South Carolina, PO Box 250504, 173 Ashley Avenue, Charleston, South Carolina |
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Abstract: | Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage (DAD) secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or noninfectious insult. We have previously described a unique animal model in which CBA/J mice infected with reovirus 1/L develop ARDS. This model recapitulates the histopathological changes observed in human ARDS, which consist of the overlapping phases of exudation, including the formation of hyaline membranes, regeneration, and healing via repair with fibrosis. In this report, we show that the development of DAD in the acute phase of the disease and intraalveolar fibrosis in the late phase of the disease was not modulated by treatment with methylprednisolone (MPS). In the presence or absence of MPS, the majority of cells infiltrating the lungs after reovirus 1/L infection were polymorphonuclear leukocytes and macrophages. A number of key proinflammatory and anti-inflammatory cytokines/chemokines that are observed in the BAL fluid of ARDS patients were also found in the lungs of mice after reovirus 1/L infection and were not modulated by MPS. These include interferon-γ, interleukin-10, and monocyte chemoattractant protein. The histopathology, cytokine/chemokine expression, and response to corticosterids in reovirus 1/L-induced ARDS are similar to what is observed in human patients, making this a clinically relevant model. |
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Keywords: | acute respiratory distress syndrome diffuse alveolar damage interferon-γ MCP-1 methylprednisolone cytokines chemokines |
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