Endothelin-1 impairs neutrophil respiratory burst and elimination of Escherichia coli in rabbits.
OBJECTIVE
During systemic inflammation, elevated levels of endothelin (ET)-1 have been reported. The aim of this study was to investigate the effects of ET-1 on neutrophil (PMN) respiratory burst, phagocytosis, and elimination of Escherichia coli from blood and tissues.


METHODS
Prospective, randomized, controlled trial.


METHODS
Experimental laboratory in a university hospital.


METHODS
A total of 18 female chinchilla rabbits.


METHODS
To quantify the clearance process, defined numbers (10(8) colony-forming units) of E. coli were injected intravenously into anesthetized rabbits, 60 mins after onset of continuous 0.2 microg/kg/min ET-1 administration (n = 9) and after saline infusion (control group, n = 9), respectively. To evaluate potential effects of ET-1 on bacterial elimination and killing, blood clearance of E. coli and colonization of different organs were investigated.


METHODS
Variables monitored were neutrophil respiratory burst and phagocytosis activity, rates of bacterial elimination from the blood, arterial blood pressure, blood gases, serum lactate concentrations, and nitrite and nitrate levels. The animals were killed 3 hrs after bacterial injection and tissue samples of liver, kidney, spleen, and lung were collected for bacterial counts.


RESULTS
Compared with the control group, ET-1 significantly impaired PMN respiratory burst (p < .05) and prolonged elimination of injected E. coli from the blood (p < .01), whereas phagocytosis functions remained unaltered. The reduced PMN burst activity after ET-1 was associated with a higher bacterial colonization of all organs (lung, p < .01; spleen, p < .05). Endothelin-1 induced increases in mean arterial pressure (p < .01) and serum lactate concentrations, whereas nitrite and nitrate levels remained unaltered.


CONCLUSIONS
Endothelin-1 impairs respiratory burst and bacterial clearance from the blood and tissue. Thus, elevated levels of ET-1 during sepsis could induce organ hypoperfusion and cause disturbances in immune functions, increasing the risk of bacterial infections.
Heller
A
A
Department of Anesthesiology, University Hospital Carl Gustav Carus, Dresden, Germany. heller-a@rcs.urz.tu-dresden.de
Schmeck
J
J
Heller
S
S
Phan
H
H
Nebe
T
T
Urbaschek
R
R
Koch
T
T
D000818:Animals; D019332:Endothelin-1 / Q000494:pharmacology*; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D011817:Rabbits; D016897:Respiratory Burst / Q000187:drug effects* / Q000276:immunology
D019332:Endothelin-1