Increased circulating concentrations of growth-related oncogene (GRO)-alpha in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory state associated with increased risk of intestinal cancers. The aim of this study is to examine serum concentrations of growth-related oncogene (GRO)-alpha, a cytokine with inflammatory and growth-regulatory properties, in patients with IBD. We measured serum concentrations of GRO-alpha in 60 patients with ulcerative colitis, 42 patients with Crohn's disease, 16 patients with other colitides, 12 patients with colorectal cancer, and 40 normal subjects using an enzyme-linked immunosorbent assay. We then analyzed how the cytokine was related to clinical and laboratory variables. Serum GRO-alpha concentrations in patients with active IBD were significantly higher than those in patients with quiescent disease, which in turn were higher than those in normal controls. Concentrations in patients with active ulcerative colitis were higher than in patients with active Crohn's disease. Analysis of paired serum samples showed a decrease in GRO-alpha after initiation of therapy. Furthermore, serum GRO-alpha correlated well with laboratory markers of IBD activity. We conclude that GRO-alpha may have an important role in development of IBD, and might itself be used as a marker of activity. Manipulation of GRO-alpha function might prove therapeutically useful.

Bifidogenic growth stimulator for the treatment of active ulcerative colitis: a pilot study.

OBJECTIVES: Experimental studies have shown that luminal antigens are involved in chronic intestinal inflammatory disorders. Bifidogenic growth stimulator (BGS) is a prebiotic preparation produced by Propionibacterium freudenreichii isolated from Swiss cheese. Previously BGS was shown to act in the colon as a growth stimulator of Bifidobacteria. This study investigated the efficacy and safety of BGS in the treatment of ulcerative colitis. METHODS: Twelve patients with mildly to moderately active ulcerative colitis received orally 4.5 g of BGS daily for 4 wk in an open-label treatment protocol while the baseline anti-inflammatory therapy was continued. The response to treatment was evaluated clinically and endoscopically. Concentrations of short-chain fatty acids and the composition of commensal bacteria, including Bifidobacteria, Enterobacteria and Bacteroides species, were studied in stool samples. RESULTS: Patients showed improvement in their clinical activity index scores, with a significant decrease in the score from 7.4 +/- 2.8 to 4.7 +/- 1.5 (mean +/- standard error of the mean, P < 0.01). The endoscopic index score decreased from 4.4 +/- 1.7 to 2.8 +/- 1.8 (P < 0.05) with treatment. Patients showed an increase in stool butyrate concentrations after BGS treatment (P < 0.05). There were no significant changes in stool levels of bacteria as a result of BGS treatment. No side effects related to BGS were observed. CONCLUSIONS: Oral BGS therapy may represent a non-toxic way to treat ulcerative colitis. However, controlled studies are needed to demonstrate its efficacy in the treatment of this disorder.

Interleukin-10 in the pathophysiology of inflammatory bowel disease: increased serum concentrations during the recovery phase.

Using a specific enzyme-linked immunosorbent assay, IL-10 concentrations were measured in serum from 62 patients with ulcerative colitis (UC), 43 with Crohn's disease (CD), 25 with other colitides, and 44 normal control subjects. Serum IL-10 concentrations were increased in patients with active UC but not in those with active CD when compared with normal control subjects. A time course study showed that in patients with UC and CD, serum concentrations of IL-6 and C-reactive protein increased during the acute phase and returned to normal as patients go into remission. Notably, serum IL-10 concentrations increased during the phase of disease resolution and declined thereafter regardless of the treatment modality. Gel filtration analysis indicated that IL-10 circulated predominantly as a dimer. In conclusion, this study shows that serum IL-10 is increased during disease recovery in patients with inflammatory bowel disease, and may be a helpful marker in monitoring disease status.

Germinated barley foodstuff, a prebiotic product, ameliorates inflammation of colitis through modulation of the enteric environment.

BACKGROUND: Germinated barley foodstuff (GBF), which contains glutamine-rich protein and hemicellulose-rich fiber, exhibits therapeutic effects in ulcerative colitis; however, its mechanism is still under investigation. The aim of this study was to evaluate the anti-inflammatory effects of GBF on colitis in terms of the epithelial inflammatory response. METHODS: Mice with dextran sulfate sodium-induced colitis were used. The effects of GBF on the colitis were evaluated by measuring the body weight; disease activity; mucosal damage (histology, mucosal inflammatory parameters, nuclear factor kappa B [NFkB] activation, and signal transducer and activator of transcription 3 [STAT3]); serum interleukin 6 (IL-6) level; cecal short-chain fatty acids (SCFAs); and bile acid contents. RESULTS: GBF significantly prevented disease activity and body weight loss after induction of colitis. Serum IL-6 level and mucosal STAT3 expression were also significantly attenuated, with a conspicuous reduction of mucosal damage; NFkB activity showed the same tendency. Cecal butyrate content was significantly higher and, interestingly, GBF mice had lower bile acid concentrations than the control group. CONCLUSIONS: GBF has the potential to reduce the epithelial inflammatory response by depressing STAT-3 expression and inhibiting NFkB binding activity. These effects may be brought about by an increase of butyrate production and adsorption of bile acids.