Modulating effect of glutamine on IL-1beta-induced cytokine production by human gut

BACKGROUND & AIMS: 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.