Modulating effect of glutamine on IL-1beta-induced cytokine production by human gut.
OBJECTIVE
Balance between pro-and anti-inflammatory mediators plays a key role in the pathogenesis and treatment of inflammatory bowel disease. Glutamine can modulate cytokine production by intestinal mucosa in healthy subjects, but studies in inflammatory states are still limited. The aim of this work was to evaluate the effects of glutamine on IL-1beta-induced cytokine production by human gut.


METHODS
Duodenal biopsies from healthy volunteers were stimulated in vitro by IL-1beta in the presence of increasing glutamine concentrations. Cytokine production was assessed in culture media by ELISA and cytokine mRNA expression in biopsies by RT-PCR. Results, in pg/mg of tissue, (median [range]), were compared by non-parametric paired tests.


RESULTS
IL-1beta stimulation increased IL-6 and IL-8, but did not affect IL-4 and IL-10 production. IL-8 and IL-6 production from stimulated biopsies significantly decreased with increasing glutamine concentration from 0.5 to 10mM, (2543 [828-3634] to 1499 [282-2617] for IL-8, 62 [22-117] to 24 [12-99] for IL-6, both P<0.05), whereas IL-10 production was increased (0.7 [0.2-1.6] to 1.2 [2.6-0.5],P<0.05). Glutamine also increased IL-10 mRNA level in biopsies (P<0.05). IL-4 production was not affected by glutamine.


CONCLUSIONS
Glutamine was shown in human intestinal mucosa to reduce the production of the pro-inflammatory cytokines IL-6 and IL-8, and enhance the production of the anti-inflammatory cytokine, IL-10.
Coëffier
M
M
Appareil Digestif Environnement et Nutrition (ADEN EA 3234) and Institut Fédératif de Recherches Multidisciplinaires sur les peptides (IFR no23), CIC-INSERM-CHU, Rouen, France.
Marion
R
R
Ducrotté
P
P
Déchelotte
P
P
D000328:Adult; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005973:Glutamine / Q000494:pharmacology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D005973:Glutamine; D016753:Interleukin-10; D015847:Interleukin-4