[Frontiers in Bioscience E4, 2584-2604, June 1, 2012]

[Frontiers in Bioscience E4, 2584-2604, June 1, 2012]

Molecular mediators of polymicrobial sepsis

Sandra Wintersteller¹, Jens Hahnhaussen², Barbara Kofler¹, Klaus Emmanuel²

1Department of Pediatrics, Laura Bassi Centre of Expertise, THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Paracelsus Medical University, A-5020 Salzburg, Austria,²Department of Surgery, Paracelsus Medical University, A-5020 Salzburg, Austria

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Animal models of sepsis: 3.1. Inhalation of endotoxins; 3.2. Injection of endotoxins; 3.3. Bacteremia; 3.4. Surgical models
4. Molecular mediators in different animal models of sepsis
5. Methods: 5.1. CASP surgery; 5.2. RNA isolation and cDNA synthesis; 5.3. Cytokines and Receptors RT2 Profiler; 5.4. Protein expression levels in lungs of septic mice; 5.5. Relative expression levels of neuropeptide mRNA in lungs of septic mice
6. Cytokines and chemokines: 6.1. Neuropeptides
7. Biomarkers in human sepsis: 7.1. Biomarkers with clinical relevance in abdominal sepsis; 7.2. Preoperative identification of patients with an increased risk of developing lethal postoperative sepsis; 7.3. Early prediction of lethal outcome during postoperative sepsis; 7.4. Successful surgical treatment of abdominal sepsis
8. Conclusion 9. Acknowledgments
10. References

1. ABSTRACT

Sepsis is still a major cause of postoperative morbidity and mortality. Numerous biochemical indicators have been evaluated regarding their potential in predicting prognosis in sepsis. Generally, one must differentiate between indicators: those for preoperative risk of lethal sepsis, those for early prediction of lethal outcome and those for evaluating effectiveness of therapy. In the past, immunomodulatory therapies developed in various animal studies failed to be successful in humans. It has been proposed that present models have to be reevaluated, and new, clinically more relevant models should be evolved. This article will give a short overview on the most common animal models and a comprehensive overview on markers for sepsis in animal models and clinical studies. The focus will be on abdominal sepsis with a mortality rate up to 80% after major surgery. Two animal models designed to closely mimic the clinical course of intra-abdominal sepsis, will be compared. Furthermore, relevant clinical parameters for predicting prognosis before and after major visceral surgery are illustrated.