Glutamine attenuates leukocyte-endothelial cell adhesion in indomethacin-induced intestinal inflammation in the rat.
BACKGROUND
Glutamine (Gln) is a major energy source for the intestinal mucosa. Its depletion results in epithelial atrophy and in bacterial translocation. Clinical substitution of this nonessential amino acid in critically ill persons results in a reduction of epithelial atrophy and in an accelerated recovery. The objective of this study was to assess the effect of Gln on leukocyte-endothelial cell interaction in an indomethacin (Indo)-induced long-lasting ileitis in Sprague-Dawley rats.


METHODS
Indo (7.5 mg/kg subcutaneously) was injected at time 0 and 24 hours later. Animals were fed with standard rat chow (ST) for 10 days until 12 hours before intravital microscopy analysis. Gln (3 g/kg body wt) was gavaged twice a day in the morning 4 hours apart (1) for 10 days between Indo administration and the experiment (ST/Gln, therapy), (2) for 14 days before Indo (Gln/ST, prophylaxis), or (3) from 14 days before Indo until the experiment (Gln/Gln, prophylaxis and therapy). Ten mesenteric venules (30 microm diameter) per animal (n = 5 per group) were observed using intravital microscopy, and the following parameters were monitored: number of adherent and emigrated leukocytes, leukocyte rolling velocity, erythrocyte velocity, venular blood flow, and shear rate. Macroscopically visible injury was scored 0 to 5.


RESULTS
Ten days after Indo treatment the macroscopic score was 3.5+/-0.4 vs. 0.6+/-0.2 of controls, and leukocyte adherence and emigration were increased (2.2-fold and 3.3-fold vs. control, respectively), whereas leukocyte rolling velocity and venular wall shear rate were reduced (both parameters to 81% of control). Glutamine prophylaxis, therapy, and the combination of both significantly attenuated macroscopic damage and prevented the microcirculatory disturbances to a similar extent. The beneficial effects of glutamine were accompanied by a normalization of fecal pH to control level, which had been lowered by Indo treatment.


CONCLUSIONS
The long-lasting Indo-induced ileitis was accompanied by macroscopic ulceration and microcirculatory disturbances. Oral therapy and prophylaxis with glutamine reduced macroscopic and microcirculatory inflammatory activity, indicating a special demand for glutamine in this type of inflammation.
Arndt
H
H
Department of Internal Medicine I, University of Regensburg, Germany.
Kullmann
F
F
Reuss
F
F
Schölmerich
J
J
Palitzsch
K D
KD
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D002448:Cell Adhesion / Q000187:drug effects; D004727:Endothelium / Q000166:cytology / Q000187:drug effects*; D005973:Glutamine / Q000494:pharmacology* / Q000627:therapeutic use; D007079:Ileitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007213:Indomethacin; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008833:Microcirculation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005973:Glutamine; D007213:Indomethacin