Identifikation von prognostischen Markern bei Patienten mit Sepsis

Die Sepsis ist trotz der Fortschritte der modernen Medizin noch immer mit einer hohen Morbidität und Mortalität behaftet. Durch die Identifikation von protektiven Faktoren, die eine schwere Verlaufsform verhindern und kausale Therapieansätze, die nicht nur Pathogene eliminieren, sondern auch das na...

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Bibliographic Details
Main Author: Regner, Wiebke
Contributors: Bals, Robert (Prof. Dr. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2015
Online Access:PDF Full Text
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Despite many efforts in modern medicine, systemic inflammatory response syndrome (SIRS) and sepsis are still linked to high morbidity and mortality. Identification of protective factors that prevent a severe course of the disease and new therapeutic strategies that do not only eliminate pathogens but support the balance between pro-inflammatory and immunosuppressive phases could improve the outcome. Vitamin D has a great importance for the innate and adaptive immune system. Vitamin D deficiency is a widespread problem. 28% of the healthy population are affected. The aim of this study was to examine serum levels of vitamin D (25-Hydroxycholecalciferol), Cathelicidin-LL-37 (protein and mRNA-level) and alpha-1-antitrypsin during SIRS and to identify potential protective factors and prognostic mark-ers. For this purpose, blood samples were taken from SIRS patients and control patients from the intensive care unit as well as from healthy controls. Serum levels were measured and clinical data, particularly APACHE-II-Score, SOFA-Score and MODS-Score were collected to define the severity of sepsis. The main finding was that SIRS patients are vitamin D deficient and have significant lower vitamin D levels than controls from the intensive care unit and healthy controls. Even among the healthy controls, only 28% had sufficient vitamin D levels. Contrary to the hypothesis that Cathelicidin-LL-37 is decreased during SIRS, increased levels (12,39 ± 9,775 ng/ml) were measured compared to controls from the intensive care unit and healthy controls. This difference could not be detected on mRNA-level so that a physiological degranulation of neutrophils during the inflammatory process might be a reason for the increased Cathelicidin-LL-37-level. Because of the increased level of Cathelicidin-LL-37, a negative correlation was observed between the vitamin D and Cathelicidin-LL-37 levels. No measurable correlation between the severity of sepsis and the vitamin D level, re-spectively the Cathelicidin-LL-37 level was found. SIRS-patients had significant higher alpha-1-antitrypsin-levels. This study cannot answer questions about the mechanisms of the observations. Whether vitamin D levels and/or Cathelicidin-LL-37 levels could be used as prognostic markers has to be answered in further studies.