Butyrate inhibits inflammatory responses through NF kappa B inhibition: implications for Crohn's disease

Background/aim-Proinflammatory cytokines are key factors in the pathogenesi s of Crohn's disease (CD). Activation of nuclear factor kappa B (NF kappa B ), which is involved in their gene transcription, is increased in the intes tinal mucosa of CD patients. As butyrate enemas may be beneficial in treati ng colonic inflammation, we investigated if butyrate promotes this effect b y acting on proinflammatory cytokine expression. Methods-Intestinal biopsy specimens, isolated lamina propria cells (LPMC), and peripheral blood mononuclear cells (PBMC) were cultured with or without butyrate for assessment of secretion of tumour necrosis factor (TNF) and m RNA levels. NF kappa B p65 activation was determined by immunofluorescence and gene reporter experiments. Levels of NF kappa B inhibitory protein (I k appa B alpha) were analysed by western blotting. The in vivo efficacy of bu tyrate was assessed in rats with trinitrobenzene sulphonic acid (TNBS) indu ced colitis. Results-Butyrate decreased TNF production and proinflammatory cytokine mRNA expression by intestinal biopsies and LPMC from CD patients. Butyrate abol ished lipopolysaccharide (LPS) induced expression of cytokines by PBMC and transmigration of NF kappa B from the cytoplasm to the nucleus. LPS induced NF kappa B transcriptional activity was decreased by butyrate while I kapp a B alpha levels were stable. Butyrate treatment also improved TNBS induced colitis. Conclusions-Butyrate decreases proinflammatory cytokine expression via inhi bition of NF kappa B activation and I kappa B alpha degradation. These anti -inflammatory properties provide a rationale for assessing butyrate in the treatment of CD.