Thioredoxin in human and experimental sepsis
| Autor: | Stefan Hofer, Junji Yodoi, Christian Bopp, Meike Goebel, Johannes Zimmermann, Peter Schemmer, Kartrin Hoffmann, Claudia Rosenhagen, Raoul Breitkreutz, Klaus Schulze-Osthoff, Markus A. Weigand, Hajime Nakamura |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Resuscitation animal structures Critical Care Thioredoxin reductase Peritonitis Inflammation Critical Care and Intensive Care Medicine Sepsis Cohort Studies Mice Thioredoxins Intensive care medicine Animals Humans Septic shock business.industry Middle Aged bacterial infections and mycoses medicine.disease Recombinant Proteins Mice Inbred C57BL Survival Rate Disease Models Animal Oxidative Stress Case-Control Studies Immunology Female medicine.symptom Thioredoxin business |
| Zdroj: | Critical care medicine. 37(7) |
| ISSN: | 1530-0293 |
| Popis: | Introduction: Thioredoxin (TRX) is assumed to be beneficial in acute inflammatory diseases because of its potent antioxidant properties and an inhibitory effect on neutrophil evasion into sites of inflammation. Objective: To compare plasma levels of thioredoxin in septic patients and to investigate the role of thioredoxin in a polymicrobial septic mouse model. Design and Interventions: A combined single-center noninterventional clinical observation study and randomized controlled experimental investigation. Setting: Intensive care unit of a university hospital and laboratories of four university hospitals. Measurements and Main Results: To evaluate the role of TRX in sepsis, we measured TRX in plasma of septic patients and compared its levels in survivors and patients who did not survive sepsis. In addition, we examined the effect of neutralization of endogenous TRX as well as of treatment with recombinant TRX in a mouse peritonitis model of cecal ligation and puncture (CLP). We found that the serum plasma levels of TRX were significantly higher in patients with sepsis compared with healthy individuals. Furthermore, nonsurvivors showed even higher TRX levels than survivors of sepsis. The CLP septic mouse model revealed that neutralization of endogenous TRX impaired survival of septic mice, whereas treatment with recombinant TRX after CLP strongly enhanced the survival of mice. Conclusions: Our results therefore demonstrate a critical role for TRX in the septic inflammatory response and suggest TRX as a potential therapeutic target for septic shock. (Crit Care Med 2009; 37:2155‐2159) |
| Databáze: | OpenAIRE |
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