LUNG EFFECTS DURING A GENERALIZED SHWARTZMAN REACTION AND THERAPEUTIC INTERVENTION WITH DEXAMETHASONE OR VITAMIN E
Autor: | Bo Koch, Thomas Sandström, David Rocksén, Anders Bucht |
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Rok vydání: | 2004 |
Předmět: |
Lipopolysaccharides
Vitamin ARDS Time Factors Neutrophils medicine.drug_class medicine.medical_treatment Down-Regulation Enzyme-Linked Immunosorbent Assay Critical Care and Intensive Care Medicine Antioxidants Dexamethasone Sepsis Mice chemistry.chemical_compound Oxygen Consumption hemic and lymphatic diseases Intensive care Animals Edema Vitamin E Medicine cardiovascular diseases Glucocorticoids Lung integumentary system business.industry respiratory system medicine.disease respiratory tract diseases Mice Inbred C57BL medicine.anatomical_structure Microscopy Fluorescence chemistry Immunology Emergency Medicine Cytokines Corticosteroid business Shwartzman Phenomenon medicine.drug |
Zdroj: | Shock. 22:482-490 |
ISSN: | 1073-2322 |
DOI: | 10.1097/01.shk.0000142254.38630.36 |
Popis: | We investigated if a two-hit shock model, commonly referred to as generalized Shwartzman reaction (GSR), can prime for indirect acute respiratory distress syndrome (ARDS) in mice. The GSR was provoked in C57BL/6 mice by two consecutive i.p. injections of 100 microg lipopolysaccharide (LPS) at t = 0 and t = 20 h. These mice demonstrated a dramatic decrease in respiratory capacity and 80% mortality after the second injection. No such effect was observed when LPS was given as a single 200 microg dose at t = 0. Increased expression of proinflammatory cytokines in serum (interleukin-1beta, interleukin-6 and interferon-gamma), lung neutrophilia, and edema formation were observed in mice injected with one dose of LPS, but notably, mice exposed twice did not further increase their inflammatory response. Early treatment 1 h after the first LPS injection (t = 1 h) with either dexamethasone (10 mg/kg) or vitamin E (50 mg/kg) improved respiratory function and down-modulated the induction of proinflammatory cytokines in serum. In conclusion, mice with a generalized Shwartzman reaction exhibited features resembling some aspects of the pathophysiology in septic ARDS, i.e., neutrophilic inflammation, edema formation, impaired respiratory capacity, and mortality. Our data indicate that a systemic cytokine response and lung neutrophilia may prime for the GSR but that other mechanisms account for the rapid decline in lung function after the second challenge. We suggest that this model can be used for studies of pathogenesis and therapeutic prevention of acute respiratory failure. |
Databáze: | OpenAIRE |
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