Hypertensive Ratten mit Antibiotika- und G-CSF Prophylaxe überleben eine abdominelle Sepsis besser als Dahl-Salz-sensitive und normotensive Wistar Ratten in klinik-modellierenden randomisierten Studien (CMRTs)

Risikofaktoren wie z.B. Diabetes mellitus, Unterernährung oder Blutverlust führen zu einer veränderten immunologischen Reaktivität gegenüber Mikroorganismen und zu einer erhöhten Mortalität in der abdominellen Sepsis, sowohl im Tiermodell als auch in der Klinik. Ebenso spielt der Risikofaktor Blutho...

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Bibliographic Details
Main Author: Tischer, Björn
Contributors: Bauhofer, Artur (Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2005
Online Access:PDF Full Text
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Table of Contents: Diabetes mellitus, malnutrition or bloodloss are potential riskfactors which lead to an disturbed immunological reaction against mikroorganismen and to an increased mortality in abdominal sepsis not only in trials with rodens but also in clinical reality. More than this, hypertension is proposed as a risk faktor in the pathogenesis of stroke and heart attack and also infections. In this trial a model of primary hypertension with spontaneous hypertensive rats (SHR) and an intermediate model induced by genetic and enviromental factors with Dahl salt sensitive (DS) rats where chosen for analysis of a G-CSF prophylaxis in rats with polymicrobial abdominal sepsis induced by peritoneal contamination an infection with standarized stool inoculum. Clinical complexity and trial conditions were simulated in clinic modelling ranomized trials (CMRTs). Different mortality rates among the groups (SHR, DS, Wistar) were observed. Hypertensive SHR rats showed a significantly lower mortality rate than normotensive Wistar rats, hypertensive DS rats showed a slight tendency of lower mortality rate than Wistar rats. The proinflammatory cytokines IL 1, IL 6 and MIP 2 in organes of lung, liver and spleen were lower in the SHR group compared to wistar rats. The anti-inflammatory cytokine IL-10 was expressed on a higher level in liver in the strain of SHR with infection compared with Wistar rats. This could be a positive influence for the SHR group whereas the lower expression of IL-10 in DS rats a more neative outcome promotes. Studying the protein levels of circulating cytokines no difference has been found between the strains of SHR and Wistar rats post infection. The local expression of cytokine seem to play a more important role than systemic ones. Hypertension itself is not the decisive factor for cytokin expression and surviving of rats with abdominal infections but rather their genetic bakground. An explanation for the higher resistance and better mortality rate of SHR rats against microbial infection and their produced toxins can be found in a distinct reduced local expression of pro-inflammatory cytokines.