Aspects on sepsis : treatment and markers

Abstract

Sepsis is one of the greatest challenges in critical care medicine today, while the treatment of sepsis and evaluation of its severity is complicated. The first part of this thesis presents two approaches on the use of antimicrobial peptides in sepsis treatment, relying on both soluble and immobilized peptides. All peptides tested, truncated from human and non-human antimicrobial peptides, did neutralize LPS activity in a dose-dependent manner. Immobilization of the peptides did not inhibit their ability to bind LPS, therefore, the peptides can be considered for extracorporeal LPS removal in sepsis therapy. Interestingly, the soluble peptides inhibited LPS induced cytokine production but potentiated LTA induced cytokine production in human blood. Consequently, care should be taken when considering these peptides in treatment of Gram-positive infections. The second part of this thesis evaluates the inflammatory marker soluble urokinase plasminogen activator receptor (suPAR) in sepsis prognosis. Also, an investigation whether suPAR can be detected in human saliva was undertaken. The results indicate that plasma levels of suPAR are increased in sepsis patients compared to controls, but there was no significant difference between survivors and non-survivors. Plasma levels of suPAR did not correlate with other inflammatory markers, suggesting that suPAR reflects general activation of the immune system rather than exerting inflammatory actions. Moreover, suPAR can be detected in saliva and the levels are more than 10 times higher than the corresponding plasma levels in healthy individuals.