The in vivo appearance of soluble interleukin (IL)-6 receptor (sIL-

Abstract:Background. Increased numbers of mast cells are found in various solid tumors. To investigate the role of mast cells in the vicinity of gastric cancer cells, we used special staining and an immunohistochemical technique. Methods. Specimens were surgically obtained from 102 patients with gastric cancer. Mast cells around the tumor edge of gastric cancer nests were counted by staining with 0.05% toluidine blue solution. Blood vessels in these areas were also counted, by immunohistochemical staining of endothelial cells for factor VIII. Results. The average number of mast cells and blood vessels in gastric cancer specimens was significantly higher than that in normal gastric tissue. Specimens from patients with advanced disease with metastases to lymph nodes had more mast cells than specimens from patients with early-stage disease. Mast cells in specimens from patients with metastatic lymph nodes were significantly increased in comparison with numbers in specimens from those without nodal metastases. Mast cell numbers in the specimens of patients with lymphatic or blood vessel invasion were significantly higher than numbers in specimens from patients without such invasion. Mast cells were localized near the new vessels around gastric cancer cells. Mast cell numbers increased as the number of blood vessels increased (correlation coefficient, 0.783). Postoperative survival curves revealed that patients with increased numbers of mast cells had a poor prognosis. Conclusions. All these results suggest that mast cell accumulation at the tumor site may lead to increased rates of tumor vascularization and, consequently, increased rates of tumor growth and metastasis.

SUMMARYIL-8 is generating increasing interest as a powerful neutrophil chemoattractant and activator. To elucidate the mechanisms of neutrophil infiltration in inflammatory bowel disease, we examined 33 patients with ulcerative colitis (UC), 18 with Crohn's disease (CD), eight with some other type of colitis, and 18 normal control subjects for measurement of IL-8 in homogenates of colonic biopsy specimens. The affected colonic mucosa was found to contain significantly more IL-8 in patients with active inflammatory bowel disease than in patients with inactive disease (UC, P<0-001; CD, P < 0-001), in patients with other types of colitis (UC, P < 0 05; CD, P < 0-0 1), or in normal control subjects (UC, P<0-001; CD, P<0-001). Colonic IL-8 levels correlated significantly with the macroscopic grade of local inflammation, especially in patients with UC (P< 0-001). Colonic IL-8 levels also correlated well with the neutrophil numbers in mucosal tissue (UC, r = 0-950, P <0-001; CD, r = 0 940, P < 0-001), and with colonic IL-1I (r = 0-91 1, P < 0-001) and tumour necrosis factoralpha (TNF-a) levels (r = 0-604, P < 0-001 ) in patients with these two conditions. These data suggest a potential role for IL-8 and its regulatory cytokines IL-1 and TNF-a in mediating neutrophil infiltration of the gut wall in inflammatory bowel disease.

Background Germinated barley foodstuff (GBF) has been shown to attenuate intestinal injury in animal models, largely by increasing luminal short‐chain fatty acid production. Aim To investigate the safety and efficacy of GBF in the treatment of ulcerative colitis (UC). Methods Ten patients with active UC received 30 g of GBF daily for 4 weeks in an open‐label treatment protocol while the baseline anti‐inflammatory therapy was continued. The response to treatment was evaluated clinically and endoscopically. Pre‐ and post‐treatment stool concentrations of short‐chain fatty acids were measured by gas‐liquid chromatography. Results Patients showed improvement in their clinical activity index scores, with a significant decrease in the score from 6.9 ± 1.4 to 2.8 ± 1.5 (mean ± S.E.M., P < 0.05). The endoscopic index score fell from 6.1 ± 2.3 to 3.8 ± 2.3 (P < 0.0001). Patients showed an increase in stool butyrate concentrations after GBF treatment (P < 0.05). No side‐effects were observed. Conclusions Oral GBF therapy may have a place in management of ulcerative colitis, but controlled studies are needed to demonstrate its efficacy in the treatment of this disorder.

There is now clear evidence supporting the role of cytokines in the clinical and immunopathological manifestations of human inflammotory bowel disease. The purpose of the present study was to determine the possible role of a cytokine network in a rat model of trinitrobenzene sulfonic acid-induced colitis and to examine its relation to intestinal permeability. After a rapid increase in the intestinal permeability of Evans blue in the colon, tumor necrosis factor-α increased transiently, and interleukin-1 and interleukin-6 followed thereafter. The majority of tumor necrosis factor-α- and interleukin-1-producing cells observed by immunofluorescent staining was revealed to be macrophages. Repeated injections of interleukin-1 receptor antagonist led to a modest decrease in myeloperoxidase activity and colon weight. These findings suggest that enhanced pro-inflammatory cytokine production from intestinal macrophages accompanied by increased intestinal permeability may contribute to intestinal and systemic features of trinitrobenzene sulfonic acid-induced colitis. Pharmacologic blockade of pro-inflammatory cytokines may help reduce intestinal inflammation.