Tumor necrosis factor-alpha-induced lung injury and its modulation by synthetic polynucleotide: a physiologic-morphometric analysis.
PolyI:C, a potent interferon (IFN) inducer, protects the isolated perfused lung (IPL) against platelet-activating factor (PAF)-induced injury. Because the release of PAF is stimulated by tumor necrosis factor (TNF), this study was designed to measure the effects of polyI:C on TNF-induced lung inflammation and injury. TNF (2.5 micrograms/kg) was administered to rabbits intravenously as continuous infusion over 2 h. PolyI:C was given intraperitoneally 16 h before TNF infusion. The rabbits were then anesthetized and sacrificed, and the lungs were ventilated with 20% O2 + 5% CO2 and perfused with buffer for 60 min. Lung weight gain was recorded continuously. After perfusion, lungs were inflation fixed for light and electron microscopy with morphometric analysis. Four groups of rabbit lungs were studied: (1) control; (2) polyI:C; (3) TNF, and (4) polyI:C + TNF. Lungs in the TNF group showed increased weight gain (15.4 +/- 2.4 g/h vs. 7.1 +/- 0.5 g/h in controls, p = .02) and increased volume of inflammatory cells (261% of control). These were mostly mononuclear cells (96%), primarily located in the interstitial and alveolar compartments (80%). In the polyI:C + TNF group, the weight gain of the IPL tended to be smaller (8.3 +/- 1.8 g/h, p = .08). Total inflammatory cell volume in the IPL remained elevated (330% of control), but mononuclear cells accounted for only 60% of the cell population. Most of these cells were found in the intravascular compartment (65%) implicating mononuclear cells in the early pathogenesis of TNF-induced pulmonary capillary injury in rabbits. PolyI:C, which attenuates TNF-induced injury, also modulates effects of TNF on mononuclear cell and granulocyte infiltration in the lung.
Duke Scholars
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Related Subject Headings
- Vascular Resistance
- Tumor Necrosis Factor-alpha
- Respiratory System
- Recombinant Proteins
- Rabbits
- Pulmonary Edema
- Pulmonary Circulation
- Poly I-C
- Peroxidase
- Perfusion
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Vascular Resistance
- Tumor Necrosis Factor-alpha
- Respiratory System
- Recombinant Proteins
- Rabbits
- Pulmonary Edema
- Pulmonary Circulation
- Poly I-C
- Peroxidase
- Perfusion