Modulation of nitric oxide and cytokines production by L-arginine in human gut mucosa.
BACKGROUND
Arginine is a conditionally essential amino-acid with immuno-modulatory properties, mainly through the nitric oxide (NO) pathway.


OBJECTIVE
To assess the effects of arginine on intestinal production of pro- and anti-inflammatory cytokines and NO in human gut.


METHODS
An enteral solution of arginine or a control solution of amino-acids was administered to 8 healthy volunteers on a randomized cross-over design. Duodenal biopsies were taken. Pro- (IL-6, IL-8) and anti-inflammatory (IL-4, IL-10) cytokines mRNA expression was assessed by RT-PCR. Other biopsies were cultured with 0.1, 0.5 or 2 mM arginine or control amino-acids, under basal or IL-1beta-induced inflammatory conditions. Interleukin-4, IL-6, IL-8 and IL-10 production was measured in culture supernatant by ELISA and NO production by Griess reaction.


RESULTS
Arginine enhanced the production of NO under inflammatory conditions in a dose-dependent manner (P=0.03). IL-1beta increased the production of IL-8 and IL-6 (P<0.01). Arginine had no effect on pro- and anti-inflammatory cytokines production both under basal and inflammatory conditions.


CONCLUSIONS
Arginine enhanced the production of NO but did not affect that of cytokines in inflammatory human gut. Further clinical studies are required to assess whether arginine-enhanced NO production plays a beneficial or deleterious effect in intestinal inflammation.
Lecleire
Stephane
S
Appareil Digestif Environnement Nutrition (ADEN EA 3234) and Institut Fédératif de Recherches Multidisciplinaires sur les peptides (IFR n 23), CIC-INSERM-CHU, 76031 Rouen Cedex, France. stephanelecleire@hotmail.com
Coeffier
Moise
M
Leblond
Jonathan
J
Hubert
Aurelie
A
Lemoulan
Sabrina
S
Petit
Andre
A
Ducrotte
Philippe
P
Dechelotte
Pierre
P
Marion
Rachel
R
D000328:Adult; D001120:Arginine / Q000008:administration & dosage*; D001706:Biopsy; D018592:Cross-Over Studies; D004386:Duodenum / Q000187:drug effects* / Q000276:immunology; D004750:Enteral Nutrition; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
D007378:Interleukins; D012333:RNA, Messenger; D009569:Nitric Oxide; D001120:Arginine