Mild versus strong anti-inflammatory therapy during early sepsis in mice: A matter of life and death*
| Autor: | Jan N. M. IJzermans, Robbert Benner, Jan Willem van den Berg, Willem A. Dik, Ron W. F. de Bruin, Marten van der Zee, Conny van Holten-Neelen, Nicole M A Nagtzaam, Jeroen Bastiaans |
|---|---|
| Přispěvatelé: | Immunology, Surgery |
| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class medicine.medical_treatment Anti-Inflammatory Agents Inflammation Critical Care and Intensive Care Medicine Dexamethasone Sepsis Mice Internal medicine Intensive care polycyclic compounds medicine Animals Kidney Dose-Response Relationship Drug business.industry medicine.disease Mice Inbred C57BL Disease Models Animal Cytokine medicine.anatomical_structure Endocrinology Bacteremia Immunology Cytokines Corticosteroid medicine.symptom business Cell Adhesion Molecules hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Critical Care Medicine, 39(6), 1275-1281. Lippincott Williams & Wilkins |
| ISSN: | 0090-3493 |
| DOI: | 10.1097/ccm.0b013e31820edf75 |
| Popis: | Objective: A recent literature-based study suggested that low-dose corticosteroid treatment has a beneficial effect on mortality in septic patients, whereas high-dose corticosteroid treatment has not. This suggests that mild down-regulation of the inflammatory response during early sepsis may be beneficial while extensive reduction of the inflammatory response is not. To investigate this hypothesis, we examined the effect of dexamethasone in varying doses on cecal ligation and puncture-induced inflammation and mortality. Design: Animal study. Setting: University research laboratory. Subjects: Male C57BL/6 mice. Interventions: Mice were subjected to cecal ligation and puncture, and dexamethasone was administered intravenously at a dosage of 0.05 (L/DEX), 0.25 (M/DEX), or 2.5 (H/DEX) mg/kg body weight 20 mins postoperatively. Mice receiving phosphate-buffered saline served as controls. Survival was recorded up to 21 days and inflammatory markers were determined in plasma, lungs, liver, and kidney at 6 hrs following cecal ligation and puncture as well as bacterial load in blood and peritoneal fluid. Measurements and Main Results: L/DEX treatment significantly improved survival compared with control mice, whereas treatment with higher concentrations of dexamethasone (M/DEX and H/DEX) did not. Treatment with either M/DEX or H/DEX was associated with significantly (p < .05) reduced cytokine plasma levels as compared with controls at 6 hrs after cecal ligation and puncture. In addition, M/DEX or H/DEX powerfully reduced cytokine messenger RNA expression in the lung, liver, and kidney. In contrast, treatment with L/DEX was associated with a mild, but nonsignificant, reduction of cytokine plasma levels. In addition, L/DEX moderately reduced cytokine messenger RNA expression in lung, liver, and kidney tissue and reduced the occurrence of bacteremia. Conclusions: A modest down-regulation of the early sepsis-associated inflammatory response improves survival in a murine cecal ligation and puncture model. We propose that the success of anti-inflammatory therapies in a septic setting fundamentally depends on finding a treatment balance that reduces the hyper-inflammation-induced pathology but still allows adequate defense against pathogens. (Crit Care Med 2011; 39:1275-1281) |
| Databáze: | OpenAIRE |
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