Alterations of neutrophil responses to tumor necrosis factor alpha and interleukin-8 following human endotoxemia
| Autor: | Carolyn J. Tindal, R C Bass, H S Bjornson, George F. Babcock, Joseph S. Solomkin |
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| Předmět: |
medicine.medical_specialty
Neutrophils medicine.medical_treatment Immunology Inflammation Microbiology Receptors Tumor Necrosis Factor Proinflammatory cytokine Internal medicine medicine Humans Interleukin 8 Receptor biology Tumor Necrosis Factor-alpha Interleukin-8 Chemotaxis Endotoxins Fibronectin Infectious Diseases Cytokine Endocrinology biology.protein Tetradecanoylphorbol Acetate Parasitology Tumor necrosis factor alpha medicine.symptom Research Article |
| Zdroj: | Europe PubMed Central |
| Popis: | Interleukin-8 (IL-8), a neutrophil chemoattractant and activating cytokine, has been implicated as a proinflammatory mediator in gram-negative sepsis. In vitro data support the notion of IL-8 as an endothelial adherence inhibitor. To evaluate this issue, we infused six volunteers with reference endotoxin and measured plasma levels of IL-8, neutrophil tumor necrosis factor alpha (TNF-alpha) receptors, TNF-alpha-induced adherence to fibronectin, and neutrophil chemotaxis to IL-8 and other attractants. We found that, at 3 h postinfusion, IL-8 but not TNF-alpha plasma levels were elevated. Neutrophils had shed L-selectin (mean channel fluorescence decrease, 79 +/- 9 to 49 +/- 7; P = 0.0625) and TNF-alpha receptors (decrease in number of receptors per cell, 1,596 +/- 340 to 574 +/- 93; P = 0.004). Cells were chemotactically desensitized to IL-8. TNF-alpha-induced adherence to fibronectin was suppressed from 69% +/- 5% of the phorbol myristate acetate response to 38% +/- 7% (P = 0.0154). These findings support the notion that release of IL-8 into the vascular space may be an in vivo mechanism for suppression of neutrophil accumulation at extravascular sites. L-Selectin loss would reduce the ability of neutrophils to adhere to activated endothelial cells. The specific loss of migratory response to IL-8 would impair neutrophil delivery to areas where IL-8 was the predominant chemoattractant. Loss of TNF-alpha-induced adherence to fibronectin would blunt those responses, including production of oxidants, capacitated by adherence. |
| Databáze: | OpenAIRE |
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