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Nutritional Immunology

Combined Glutamine and Arginine Decrease Proinflammatory Cytokine Production by Biopsies from Crohn's Patients in Association with Changes in Nuclear Factor-B and p38 Mitogen-Activated Protein Kinase Pathways^1–3,

⁴ Appareil Digestif Environnement Nutrition EA4311, Institute for Biomedical Research, IFRMP23, Rouen University and Rouen University Hospital, Rouen, France and ⁵ Department of Gastroenterology and Nutrition, Rouen University Hospital, Rouen, France

Glutamine (Gln) and arginine (Arg) are conditionally essential amino acids with immunomodulatory properties. The aim of the study was to assess the effects of Gln and Arg alone or in combination on cytokine release by cultured colonic biopsies from patients with active Crohn's disease (CD). Ten consecutive patients [mean (range) age 26 (18–39) y] with active colonic CD (mean CD activity index: 383.7 ± 129.8) were prospectively included in the study. Eight colonic biopsies were obtained via a colonoscopy and incubated during 18 h with low (physiological) or high (pharmacological) doses of Arg (0.1 or 2 mmol/L designated as Arg^low or Arg^high, respectively) and Gln (0.6 or 10 mmol/L designated as Gln^low or Gln^high, respectively). The concentrations of cytokines [interleukin (IL)-4, IL-10, IL-8, IL-6, tumor necrosis factor- (TNF), IL-1β, interferon-) were assessed by ELISA, and nitric oxide (NO) production was evaluated by Griess assay. Nuclear factor (NF)-B p65 subunit, inhibitor of NFB-, and p38 mitogen-activated protein kinase (MAPK) were assessed by immunoblotting. Arg^high/Gln^high decreased the production of TNF, IL-1β, IL-8, and IL-6 (each P < 0.01). Arg^low/Gln^high decreased IL-6 and IL-8 production (both P < 0.01), whereas Arg^high/Gln^low did not affect cytokine and NO production. Arg^low/Gln^high and Arg^high/Gln^high decreased NF-B p65 subunit expression, whereas p38 MAPK was decreased only by Arg^high/Gln^high. Combined pharmacological doses of Arg and Gln decreased TNF and the main proinflammatory cytokines release in active colonic CD biopsies via NF-B and p38 MAPK pathways. These results could be the basis of prospective studies evaluating the effects of enteral supply of combined Arg and Gln during active CD.

^* To whom correspondence should be addressed. E-mail: pierre.dechelotte{at}chu-rouen.fr.

Manuscript received 3 September 2008. Initial review completed 24 September 2008. Revision accepted 29 September 2008.