Regulation of Adhesion Molecules during Human Endotoxemia
| Autor: | Hans-Georg Eichler, Barbara Vondrovec, Jean Amiral, Oswald Wagner, Volker Richter, Petra Stohlawetz, Thomas Pernerstorfer, Bernd Jilma, Andrew D. Blann |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Adult
Lipopolysaccharides Male Pulmonary and Respiratory Medicine Lipopolysaccharide Neutrophils Thrombomodulin Intercellular Adhesion Molecule-1 Vascular Cell Adhesion Molecule-1 Pharmacology Critical Care and Intensive Care Medicine Monocytes Sepsis Leukocyte Count chemistry.chemical_compound Bolus (medicine) Double-Blind Method von Willebrand Factor Blood plasma medicine Humans L-Selectin Acetaminophen Aspirin Tumor Necrosis Factor-alpha Septic shock Cell adhesion molecule business.industry Anti-Inflammatory Agents Non-Steroidal medicine.disease Endotoxemia P-Selectin chemistry Immunology business Cell Adhesion Molecules medicine.drug |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine. 159:857-863 |
| ISSN: | 1535-4970 1073-449X |
| DOI: | 10.1164/ajrccm.159.3.9805087 |
| Popis: | Gram-negative septic shock is mediated in part by endotoxin (lipopolysaccharide; LPS), and animal models have shown that blockade of even single adhesion molecules considerably improves survival. Thus interference with the adhesion cascade may provide a useful therapeutic approach in human sepsis. Young healthy men (n = 30) each received a bolus of 4 ng/kg LPS intravenously to study the effects of endotoxemia on adhesion processes in humans and to identify potential targets for pharmacologic intervention. One third of subjects received pretreatment with 1,000 mg aspirin and 1,000 mg paracetamol to study potential antiinflammatory effects of aspirin or effects of antipyresis. Circulating neutrophils dropped by -80% at 67 min after LPS, monocytes by -96% at 90 min, and lymphocytes by -85% at 240 min. L-selectin expression decreased, particularly on monocytes. Circulating (c)E-selectin levels increased by 820%, von Willebrand factor-Ag (vWF), soluble thrombomodulin, circulating (c)P-selectin, circulating intercellular adhesion molecule-1 (cICAM-1), and circulating vascular cell adhesion molecule-1 (cVCAM-1) by a mean of 65 to 98% (p0.001 for all), but cL-selectin by only 15%. Urinary excretion of soluble adhesion molecules was negligible. Aspirin had no influence on the LPS-induced changes of adhesion parameters, but paracetamol blunted the relative increase in vWF while having no effects on the other parameters measured. The consistent, profound, and early upregulation of cE-selectin during endotoxemia indicates that cE-selectin may be a better surrogate marker to monitor the activation status of endothelial cells in systemic inflammation than the other markers measured. Although aspirin did not have any antiinflammatory effects in this model, paracetamol lowered the relative increase in vWF. |
| Databáze: | OpenAIRE |
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