Synergistic effects of tumour necrosis factor and morphine on gut barrier function.
OBJECTIVE
To study the effects of tumour necrosis factor (TNF) and morphine on intestinal permeability, intestinal transit and bacterial translocation in the rat.


METHODS
A randomized interventional controlled experiment.


METHODS
University surgery and microbiology research laboratory.


METHODS
Forty-four rats in five groups as follows: control (n = 9); treated with morphine every 2 hours for 8 hours (n = 9); treated with TNF for 5 minutes (n = 10); treated with TNF plus morphine every 2 hours for 8 hours (n = 6); and treated with TNF plus morphine every 3 hours for 24 hours (n = 10).


METHODS
Intestinal permeability as measured by the uptake of chromium-51 ethylenediaminetetraacetate (51Cr-EDTA) over 8 hours, intestinal transit as measured by the amount of 51Cr-EDTA remaining in the gastrointestinal tract at the time of animal sacrifice, intestinal bacteria counts and translocation of bacteria as measured from bacterial counts of mesenteric lymph nodes, spleen and liver at the time of sacrifice.


RESULTS
Morphine increased intestinal transit time and ileal bacteria counts (p < 0.05). TNF alone did not increase intestinal permeability or bacterial translocation. TNF plus morphine increased intestinal transit time, intestinal permeability, bacterial counts and bacterial translocation (p < 0.05).


CONCLUSIONS
Morphine or increased intestinal transit time, or both, increases the concentration of intestinal bacteria. Morphine plus TNF increases intestinal bacteria counts, intestinal permeability and bacterial translocation. Morphine alone does not increase intestinal permeability or bacterial translocation.
Leslie
K A
KA
Department of Surgery, University of Western Ontario, London.
Behme
R
R
Clift
A
A
Martin
S
S
Grant
D
D
Duff
J H
JH
D000704:Analysis of Variance; D000818:Animals; D016009:Chi-Square Distribution; D015169:Colony Count, Microbial / Q000706:statistics & numerical data; D004357:Drug Synergism; D005772:Gastrointestinal Transit / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000382:microbiology; D007408:Intestinal Absorption / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000382:microbiology; D008198:Lymph Nodes / Q000187:drug effects / Q000382:microbiology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D009020:Morphine