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Glutamine Attenuates Leukocyte-Endothelial Cell Adhesion in Indomethacin-Induced Intestinal Inflammation in the Rat

Department of Internal Medicine I, University of Regensburg, Regensburg, Germany

Frank Kullmann, MD

Department of Internal Medicine I, University of Regensburg, Regensburg, Germany

Friedrich Reuß, PhD

Department of Applied Physiology, University of Ulm, Germany

Jürgen Schölmerich, MD

Department of Internal Medicine I, University of Regensburg, Regensburg, Germany

Klaus-Dieter Palitzsch, MD

Department of Internal Medicine I, University of Regensburg, Regensburg, Germany

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 µm 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. (Journal of Parenteral and Enteral Nutrition 23:12-18, 1999)

Journal of Parenteral and Enteral Nutrition, Vol. 23, No. 1, 12-18 (1999)
DOI: 10.1177/014860719902300112


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