Missing effects of zinc in a porcine model of recurrent endotoxemia.
BACKGROUND
Chronic human sepsis often is characterised by the compensatory anti-inflammatory response syndrome (CARS). During CARS, anti-inflammatory cytokines depress the inflammatory response leading to secondary and opportunistic infections. Proved in vitro as well as in vivo, zinc's pro-inflammatory effect might overcome this depression.


METHODS
We used the model of porcine LPS-induced endotoxemia established by Klosterhalfen et al. 10 pigs were divided into two groups (n = 5). Endotoxemia was induced by recurrent intravenous LPS-application (1.0 microg/kg E. coli WO 111:B4) at hours 0, 5, and 12. At hour 10, each group received an intravenous treatment (group I = saline, group II = 5.0 mg/kg elementary zinc). Monitoring included hemodynamics, blood gas analysis, and the thermal dilution technique for the measurement of extravascular lung water and intrapulmonary shunt. Plasma concentrations of IL-6 and TNF-alpha were measured by ELISA. Morphology included weight of the lungs, width of the alveolar septae, and rate of paracentral liver necrosis.


RESULTS
Zinc's application only trended to partly improve the pulmonary function. Compared to saline, significant differences were very rare. IL-6 and TNF-alpha were predominately measured higher in the zinc group. Again, significance was only reached sporadically. Hemodynamics and morphology revealed no significant differences at all.


CONCLUSIONS
The application of zinc in this model of recurrent endotoxemia is feasible and without harmful effects. However, a protection or restoration of clinical relevance is not evident in our setting. The pulmonary function just trends to improve, cytokine liberation is only partly activated, hemodynamics and morphology were not influenced. Further pre-clinical studies have to define zinc's role as a therapeutic tool during CARS.
Krones
Carsten J
CJ
Department of Surgery, Technical University of Aachen, Pauwelsstr. 30, 52074 Aachen, Germany. ckrones@ukaachen.de
Klosterhalfen
Bernd
B
Anurov
Michael
M
Stumpf
Michael
M
Klinge
Uwe
U
Oettinger
Alexander P
AP
Schumpelick
Volker
V
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000188:drug therapy*; D015633:Extravascular Lung Water / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000503:physiopathology*; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides; D009942:Organometallic Compounds / Q000627:therapeutic use*; D012008:Recurrence; D012129:Respiratory Function Tests; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015032:Zinc / Q000627:therapeutic use*; D017967:Zinc Compounds
D015850:Interleukin-6; D008070:Lipopolysaccharides; D009942:Organometallic Compounds; D014409:Tumor Necrosis Factor-alpha; D017967:Zinc Compounds; C106152:zinc-bis(hydrogenaspartate); D001224:Aspartic Acid; D015032:Zinc