The effect of treatment on lymphokine-secreting cells in the intestinal mucosa of children with Crohn's disease.

BACKGROUND: Recent studies have shown both interleukin 2 (IL-2) and interferon gamma (IFN) to be elevated in patients with active Crohn's disease compared to ulcerative colitis or non-inflammatory bowel disease controls. However the effect of treatment on these lymphokines has not been studied. PATIENTS AND METHODS: Using a reverse haemolytic plaque assay the percentage of lymphokine-secreting cells was determined in the intestinal mucosa of children with Crohn's disease before and after 8 weeks of treatment with either enteral nutrition, cyclosporin or steroids. RESULTS: Before treatment, a high percentage of cells isolated from mucosal biopsies secreted IL-2 or interferon-gamma. Eight weeks' treatment with the immunosuppressive agents cyclosporin, or with corticosteroids, produced a significant reduction in the percentage of IL-2 secreting cells, although only for the former was there also a reduction in interferon-gamma secreting cells. Enteral nutrition however, produced a reduction in lymphokine-secreting cells equivalent to cyclosporin and produced the best histological and clinical improvement. CONCLUSION: Enteral nutrition and cyclosporin can down-regulate lymphokine secretion in the gut in Crohn's disease.

Diarrhoeal disease: current concepts and future challenges. Intestinal cytokines in inflammatory bowel disease and invasive diarrhoea.

In the intestine large numbers of bacteria and their products are separated by a single epithelial layer from resident inflammatory cells (macrophages and lymphocytes). Many of these bacterial products, such as lipopolysaccharides and peptidoglycans, are potent stimulators of free radical and inflammatory cytokine production by macrophages. This can occur in vivo in response to mucosal invasion by enteropathogenic bacteria or because of inappropriate activation of these cells, as in chronic inflammatory bowel disease. In this review we present evidence for production of cytokines in normal intestine and in intestinal inflammatory conditions. The adverse effects of cytokine production upon intestinal homeostasis, in particular disruption of epithelial integrity and prothrombotic changes in the vascular endothelium, are also discussed.

Endoscopic assessment of the colonic response to corticosteroids in children with ulcerative colitis.

Twenty children with active ulcerative colitis were assessed before and after 8 weeks of medical therapy with 5-aminosalicylic acid (5-ASA) derivatives and corticosteroids. Local therapy was given for distal disease (seven cases); other disease was treated with oral prednisolone (1-2 mg/kg/day, maximum 40 mg). Eighteen of the children showed a clinical improvement on therapy, and complete remission of clinical disease activity by 8 weeks was seen in 17 (85%). C-reactive protein was elevated initially in 10 of 20 children and returned to normal posttreatment in all but one. Reassessment of the colon after treatment showed an improved endoscopic appearance in 15 and complete remission in eight (40%). Histological improvement was seen in 13, with full remission in only three (15%). In conclusion, remission of clinical disease activity by corticosteroid therapy in ulcerative colitis may not be accompanied by endoscopic remission and uncommonly by mucosal healing. This finding may be important prognostically because of the risk of dysplasia in long-standing persistent mucosal inflammation.

Tumor necrosis factor alpha-producing cells in the intestinal mucosa of children with inflammatory bowel disease.

BACKGROUND/AIMS: Cytokines are thought to be important in mediating tissue damage in inflammatory bowel disease (IBD). Many of the in vivo activities of tumor necrosis factor alpha (TNF-alpha) match the changes found in IBD, but its importance is controversial. METHODS: A sensitive, reverse hemolytic plaque assay was used to determine the frequency of TNF-alpha secreting cells isolated from mucosal biopsy specimens of children with Crohn's disease or ulcerative colitis (UC) and non-IBD controls before and after medical treatment. RESULTS: Frequency of TNF-alpha secreting cells was significantly increased in biopsy specimens from children with mild, nonspecific inflammation compared with those with histologically normal intestine. Frequency did not increase in UC compared with children with nonspecific inflammation but was significantly greater in Crohn's disease than in UC. After treatment, the frequency of TNF-alpha secreting cells was reduced in patients receiving cyclosporin A, not reduced in patients with steroids or enteral nutrition, and not changed with treatment in UC. CONCLUSIONS: TNF-alpha secreting cells are increased in the mucosa of inflamed intestine, regardless of pathogenesis. In patients with IBD, higher levels are seen in Crohn's disease than in UC, probably reflecting the extensive T-cell activation in Crohn's disease. No relation existed between histological healing and the frequency of TNF-alpha-secreting cells.