Modulation of host defense by hydrocortisone in stress doses during endotoxemia.
OBJECTIVE
To investigate the effects of low-dose hydrocortisone (HC) on neutrophil respiratory burst, phagocytosis, and elimination of E. coli from blood and tissue under endotoxemic and non-endotoxemic conditions. DESIGN. Randomized, controlled trial.


METHODS
Experimental laboratory, university hospital.


METHODS
Forty-eight female chinchilla rabbits ( n=8 in six groups A-F).


METHODS
In order to quantify the bacterial clearance process, defined numbers [10(8) colony forming units (CFU)] of Escherichia coli were injected intravenously into all anesthetized rabbits. Group A did not receive further intervention. Group B received bolus administration of HC 1.4 mg/kg and group C 14 mg/kg. Endotoxin (LPS, 40 microg/kg/h) was given to groups D, E, and F. Group E received additional bolus administration of HC 1.4 mg/kg and group F 14 mg/kg. All HC groups (B, C, E, and F) were continuously infused with HC 0.18 mg/kg/h.


METHODS
Monitored parameters were neutrophil respiratory burst and phagocytosis activity, rates of bacterial elimination from the blood, arterial blood pressure, serum lactate and LPS concentrations, as well as nitrite and nitrate levels. Tissue samples of liver, kidney, spleen, and lung were collected for bacterial counts.


RESULTS
In controls HC significantly delayed elimination of injected E. coli from the blood (P<0.01). LPS also prolonged bacterial elimination but additional HC did not further delay removal of E. coli from the blood. Under endotoxemia HC depressed respiratory burst, whereas phagocytosis functions remained unaltered. Moreover, bacterial colonization of organs was reduced after HC in the LPS groups. Significance, however, was reached only in the liver (P<0.05). Due to HC, clearance from LPS (P<0.01) and lactate (P<0.05) were improved. Levels of nitrite and nitrate did not differ among the groups.


CONCLUSIONS
HC demonstrated immunomodulatory effects even in stress doses. In endotoxemic states use of low-dose HC seems to be favorable, although not in non-septic conditions.
Heller
Axel R
AR
Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Fetscherstrasse 74, 01309 Dresden, Germany. axel.heller@mailbox.tu-dresden.de
Heller
Susanne C
SC
Borkenstein
Annette
A
Stehr
Sebastian N
SN
Koch
Thea
T
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D004731:Endotoxins / Q000378:metabolism; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006854:Hydrocortisone / Q000008:administration & dosage*; D019344:Lactic Acid / Q000097:blood; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D010587:Phagocytosis / Q000187:drug effects*; D011817:Rabbits; D012016:Reference Values
D015415:Biomarkers; D004731:Endotoxins; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D019344:Lactic Acid; D006854:Hydrocortisone