CD14 expression on monocytes and soluble CD14 plasma levels in correlation to the promotor polymorphism of the endotoxin receptor CD14 gene in patients with inactive Crohn's disease.

BACKGROUND/AIMS: The association of the single nucleotide polymorphism in the promotor of the lipopolysaccharide receptor CD14 gene (T/C at position -159) with Crohn's disease has recently been demonstrated. This CD14 polymorphism is a potential predisposition factor responsible for inter-individual differing inflammatory reactions involving the CD14 receptor. We studied the correlation between the CD14 genotype (CC, CT, TT) and the membrane-bound CD14 monocyte expression and soluble CD14 in patients with inactive Crohn's disease. METHODOLOGY: In 23 patients and 29 healthy volunteers the membrane-bound CD14 density on unstimulated monocytes and soluble CD14 plasma levels were examined using quantitative flow cytometry and enzyme-linked immunosorbent assay. RESULTS: In normal controls membrane-bound CD14 monocyte density did not differ significantly between the genotypes CC, CT, or TT. In contrast, patients with inactive Crohn's disease and genotype TT showed a significantly lower membrane-bound CD14 density on monocytes compared to patients with genotype CC. Soluble CD14 plasma levels were significantly higher in patients with inactive Crohn's disease compared to the same genotype of healthy controls, but there was no significant difference between the genotypes CC, CT, and TT. CONCLUSIONS: Our data show that the membrane-bound CD14 monocyte expression and the soluble CD14 plasma levels in patients with inactive Crohn's disease completely differ from that in healthy individuals. In order to develop individualized therapy strategies further studies should be carried out to evaluate whether the TT genotype is associated with differences in the clinical course of Crohn's disease and in the response to antibacterial treatment.

Effects of intraduodenal application of peppermint oil (WS(R) 1340) and caraway oil (WS(R) 1520) on gastroduodenal motility in healthy volunteers.

Enteric-coated preparations containing a fixed peppermint oil/caraway oil combination (e.g. Enteroplant(R)) are widely used in patients with functional dyspepsia. The effect of a separate intraduodenal application of the active ingredients of Enteroplant(R) (90 mg peppermint oil (WS(R) 1340), 50 mg caraway oil (WS(R) 1520) per capsule) and of a hydrophobic phase galenic auxiliary material contained in the Enteroplant(R) formulation (dose as contained per capsule) on gastroduodenal motility were studied with stationary manometry in healthy volunteers. The carrier demanded by the experimental setup also served as a control. The results showed that: (1) during phase III of the migrating motor complex (MMC) the frequency and duration of contractions showed a significant decrease in the duodenum for WS(R) 1340; (2) WS(R) 1520 significantly reduced the contraction amplitudes in the duodenum during phase I and II of the MMC; (3) trends for decreased values were seen for WS(R) 1340 in the gastric corpus and duodenum and for WS(R) 1520 in the gastric antrum; (4) in the gastric corpus the duration of contractions was significantly reduced after application of WS(R) 1340 during phases I and II of the MMC; (5) WS(R) 1520 significantly reduced the contraction amplitudes and the duration of contractions in the gastric corpus during phase III of the MMC; (6) for the hydrophobic phase a moderate but significant decrease of duration of contractions in the duodenum and of frequency of contractions in the gastric corpus was seen. No adverse events were observed during the study. In conclusion, it could be shown that both WS(R) 1340 and WS(R) 1520 contribute to the efficacy of Enteroplant(R). They act locally in the stomach and duodenum to produce smooth-muscle relaxation. The effects of the active ingredients WS(R) 1340 and WS(R) 1520 substantially exceed the effects observed with the galenic auxiliary material and the carrier, respectively.

Immunohistochemical localization of vascular endothelial growth factor in colonic mucosa of patients with inflammatory bowel disease.

BACKGROUND/AIMS: Significantly enhanced serum levels of VEGF (vascular endothelial growth factor) were found in patients with inflammatory bowel disease. Peripheral blood mononuclear cells have been identified as one of the origins of the circulating VEGF. The present investigation examines the localization of VEGF at the site of inflammation in colonic mucosa of patients with Crohn's disease and ulcerative colitis. METHODOLOGY: Immunohistochemical localization of VEGF and immunostaining for leukocytes were performed in colonic mucosal biopsies of 41 patients with Crohn's disease, 26 patients with ulcerative colitis and normal mucosal specimens of 5 patients with irritable bowel syndrome. Measurement of immunohistochemical staining for VEGF and for leukocytes within the epithelium and the lamina propria was performed separately by area morphometry using a computerized cell analysis system. RESULTS: In both patients with Crohn's disease and ulcerative colitis immunohistochemical staining for VEGF within the lamina propria of inflamed colonic mucosa was significantly higher compared with noninflamed mucosa (Crohn's disease: 4.26% vs. 0.07%, P < 0.001; ulcerative colitis: 3.68% vs. 0.32%, P = 0.001). There was a significant correlation between immunostaining for leukocytes and VEGF within the lamina propria in both patients with Crohn's disease (r = 0.73, P < 0.05)) and ulcerative colitis (r = 0.67, P < 0.05). In Crohn's disease immunostaining for VEGF within the epithelium was significantly higher in inflamed mucosa compared with noninflamed mucosa (9.85% vs. 0.63%, P < 0.001). In contrast, strong immunostaining for VEGF has been observed in the epithelium of noninflamed mucosa (7.60%, P < 0.003), as well as in inflamed mucosa of patients with active ulcerative colitis (9.68%, P < 0.002) compared with noninflamed mucosa of patients with inactive ulcerative colitis (1.39%). CONCLUSIONS: The present data indicate, that the increased VEGF expression within the epithelium and the interstitial accumulation of VEGF-producing leukocytes in inflamed mucosa may play an important role in the inflammatory mechanisms of Crohn's disease and ulcerative colitis.